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Dr. Kim, thank you so much for this excellent presentation and your updates. I’m a new NP in the field of cancer and this is the first time information regarding BC is making sense. I saved you videos and keep checking them for updates. Is it safe to assume that you will keep platin updates as they become available - under the comments section? Please please do not give up on your page! You are the first person who made tremendous difference on my learning because your videos are so informative. God bless you and your work!!!
I mentioned that breast cancer screening is a controversial issue. Now NCCN threw another controversy: The new NCCN guidelines state that women should undergo a breast cancer risk assessment starting at age 25 years, and they emphasize annual mammography screening beginning at age 40 years for those with average risk. The new NCCN guideline also states that earlier start may be recommended for those with additional risk factors, and screening is also important for those who are pregnant or breastfeeding.
In March 2022, olaparib was approved by FDA for adjuvant treatment for patients with high-risk HER 2(-) early breast cancer and germline BRCA mutations. Now in July 2022, it was recommended by The European Medicines Agency’s Committee for Medicinal Products in Human Use.
The FDA has approved trastuzumab deruxtecan (Enhertu) for the treatment of patients with unresectable or metastatic HER2-low breast cancer on August 5, 2022. This is the first therapy approved for HER2-low breast cancer, a newly defined subset of HER2-negative breast cancer in which there are some HER2 proteins on the cell surface, but not enough to warrant classification as HER2-positive cancer. The indication is for patients who have received prior chemotherapy in the metastatic setting or for patients whose cancer has returned during adjuvant chemotherapy or within 6 months of completing it. This approval is based on DESTINY-Breast04, a randomized, multicenter, open label clinical trial that enrolled 557 adult patients with unresectable or metastatic HER2-low breast cancer. The trial included two cohorts: 494 hormone receptor positive (HR+) patients and 63 hormone receptor negative (HR-) patients. Of these patients, 373 randomly received Enhertu by intravenous infusion every three weeks and 184 randomly received physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel or paclitaxel). The results showed improvement in both progression-free survival and overall survival in people with unresectable or metastatic HER2-low breast cancer. The median age of trial participants was 57 years old, ranging from 28 to 81 years of age. Among the 557 patients, 24% were age 65 or older. Females comprised 99.6% of the trial population. Trial participants’ race was reported as 48% White, 40% Asian, 2% Black or African American, and 3.8% Hispanic/Latino. The most common adverse reactions in patients receiving Enhertu in DESTINY-Breast04 are nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain and diarrhea. The prescribing information includes a boxed warning to advise health care professionals of the risk of interstitial lung disease and embryo-fetal toxicity. Enhertu is not recommended for women who are pregnant.
Trastuzumab Deruxtecan Improves PFS in Patients with HER2-Low Metastatic Breast Cancer (after progression over previous endocrine therapy): Destiny Breast06 study meetings.asco.org/abstracts-presentations/238015
NCCN guidelines include fluoroestradiol F18 (FES) PET scan for evaluation of ER positive recurrent or metastatic breast cancer in August 2023. However, this imaging study has been approved in 2020 by FDA. I also described fluoroestradiol F18 (FES) PET scan in the presentation.
Axillary lymph node dissection is NOT necessary for 1 or 2 sentinel lymph nodes positive early breast cancer (NCCN and ASCO guidelines): The ACOSOG Z0011 Trial (JAMA 2017 Sep 12;318): Among patients with T1 or T2 (< 5cm), 1 or 2 Sentinel LNs containing metastases, 10-Vr overall survival was not inferior for patients who had Sentinel LN Biopsy alone when compared with those who underwent axillary LN dissection (AND) after Sentinel LN Biopsy. • This study included both pre-and post-menopausal women. • This study only included patients who had breast conservation therapy (lumpectomy + radiation therapy). Therefore, patients who had mastectomy still need ALND for (+) axillary LNs metastases However, the AMAROS Trial revealed that axillary radiation was as effective as AND in regional recurrence and overall survival rates at 10-yrs, but with less lymphedema (15% vs 30%)- presented at San Antonio Breast Cancer Symposium 12/2018.
I mentioned earlier that sacituzumab gavitecan was approved by FDA for triple (-) metastatic breast cancer. I also mentioned that TROPiCS-02 trial result showed improved DFS (and OS). Now, On February 3, 2023, the FDA approved sacituzumab govitecan-hziy (Trodelvy) for patients with unresectable locally advanced or metastatic HR(+) HER-2(-) breast cancer who have received endocrine-based therapy and at least two additional systemic therapy including one chemotherapy. It’s based on TROPiCS-2 trial: ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA1001 TROPiCS-02 took patients who had received two to four prior lines of chemotherapy for metastatic hormone receptor-positive breast cancer and randomized them to get sacituzumab or to get treatment of physician's choice of chemotherapy. The study found that the patients receiving sacituzumab had a longer progression-free survival, longer overall survival, and a higher response rate. This really means for patients who've had prior endocrine therapy and a CDK4/6 inhibitor, and at least one prior chemotherapy regimen for their metastatic disease, this is now a new standard therapy option. Sacituzumab is administered weekly IV: 2 weeks in a row and then a week off. Side effects: hair loss; usually mild diarrhea, and neutropenia.
Fulvestrant vs. anastrazole for metastatic ER+ HER2- breast cancer: The choice of fulvestrant as endocrine therapy did not significantly improve overall survival (OS) compared to anastrozole among postmenopausal patients with HR-positive advanced breast cancer who were naive to endocrine therapy, according to the final analysis of the FALCON study presented at ESMO Congress 2023. The initial analysis of FALCON met its primary endpoint by showing a statistically significant improvement in progression-free survival for patients assigned to fulvestrant rather than anastrozole. However, the improvement was limited to patients with non-visceral disease (hazard ratio [HR] = 0.59; 95% CI, 0.42-0.84). The study included data from 462 patients with locally advanced or metastatic breast cancer. Among the full cohort, patients assigned to fulvestrant had a median OS of 44.8 months compared with 42.7 months for patients assigned to anastrozole. Among patients with non-visceral disease, assignment to fulvestrant correlated with a 15% reduction in the risk of death (median, 65.2 months vs 47.8 months). However, the difference did not reach statistical significance (HR = 0.85; 95% CI, 0.6-1.2). For patients with visceral disease, there was no significant improvement in OS associated with fulvestrant (median, 37.2 months vs 40.7 months).
The combination of palbociclib and fulvestrant did not prolong progression-free survival compared to fulvestrant alone in patients with hormone receptor-positive/HER2-negative metastatic breast cancer who had disease progression on prior treatment with a CDK4/6 inhibitor and endocrine therapy, according to findings from the PACE study presented at the 2022 San Antonio Breast Cancer Symposium.1 However, the study also showed that the triplet combination of the PD-L1 inhibitor avelumab with palbociclib and fulvestrant arm led to a doubling in progression-free survival.
In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.
Using the Oncotype DX Breast DCIS Score test, a laboratory test that estimates DCIS recurrence risk, may help identify patients with low-risk DCIS who can safely avoid adjuvant radiation after surgery, according to new research (abstract GS03-01) presented on December 8 at the 2023 San Antonio Breast Cancer Symposium. Researchers found that the Oncotype DX score helped identify patients who are at low and high risk for DCIS recurrence. Low-risk patients who skipped adjuvant radiotherapy after breast-conserving surgery demonstrated similar 5-year recurrence rates compared with high-risk patients who received adjuvant radiotherapy. However, to be accepted as the standard of care, it needs larger and better trials as well as longer follow-up to confirm this less-is-more approach.
New drug for metastatic breast cancer: On 1/27/23, FDA approved elacestrant (Orserdu) for postmenopausal women or men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer that progressed on at least one line of endocrine therapy including CDK4/6 inhibitors. When compared with fulvestrant or aromatase inhibitors, it improved progression free survival by 2 months (3.8 vs. 1.9 months). Dose: 345 mg by mouth a day Side effects: hyper cholesterol and triglycerides; musculoskeletal pain, liver dysfunction (for moderate liver disease, dose needs to be reduced) ESR1 receptor mutation is tested by Guardant360 CDX.
Capivasertib + endocrine therapy was recently approved for Horome Receptor + HER2- metastatic breast cancer which has + AKT1 or PIK3CA mutation as a second line therapy. ASCO issued a rapid recommendation update, published in the Journal of Clinical Oncology, regarding the use and timing of endocrine and targeted therapies for patients with HR-positive, HER2-negative metastatic breast cancer. The updated recommendations build upon clinical practice guidelines originally published in July 2021. This update was based on results from the CAPItello-291 study, a phase 3 clinical trial evaluating fulvestrant plus capivasertib in patients with metastatic breast cancer. Capivasertib is an AKT pathway inhibitor, and the study included patients with AKT1, PIK3CA, and PTEN alterations. Following results of the study, the FDA approved capivasertib, along with a companion diagnostic, in November 2023. The panel recommended that patients with HR-positive, HER2-negative breast cancer should receive multiple lines of endocrine therapy, usually in combination with targeted therapies. Genomic testing for activating mutations should be regularly performed. CDK4/6 inhibitors should be paired with endocrine therapy in the first line, while second- and third-line therapy should be determined through genomic testing. Capivasertib plus endocrine therapy was recommended for patients whose tumors harbor PIK3CA or AKT1 mutations or PTEN inactivation. Patients with PIK3CA mutations can be considered for treatment with alpelisib, but patients with AKT1 mutations should not be. “There are no comparative efficacy data for choosing a PIK3CA targeted option for those who are potential candidates for capivasertib or alpelisib treatment,” the panelists wrote. “For such patients, the panel recommends selecting the targeted agent based on perceived risk-benefit considerations such as hyperglycemia, diarrhea, or treatment discontinuation for adverse events.” The panel noted that grade 3 diarrhea and rash occurred more commonly with capivasertib (9.3% vs 6.7% and 12.1% vs 9.9%, respectively) but that hyperglycemia was more common among patients treated with alpelisib (36.6% vs 2.3%). Antihistamines, anti-diarrheal agents, and supportive care measures can be employed to mitigate potential symptoms caused by these adverse events. Everolimus can be considered for all patients regardless of tumor genomics. Monotherapy with elacestrant can be considered for patients with tumors harboring an ESR1 mutation. “While newer agents have been added to the armamentarium, there remain few studies on the optimal timing or sequence of treatments, comparisons of targeted agents within a class, or studies that compare one class of agents against another,” the panel concluded. “Such trials are an important clinical priority, as are studies to mitigate side effects of these agents.”
Breast, ovarian, prostate, and pancreatic cancers are associated with pathogenic variants in BRCA1 and BRCA2 as mentioned in the presentation. Now, it was found that more cancer types are associated with BRCA 1 and 2. Pathogenic variants in BRCA1 were associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer. The study results suggest that the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than that determined from previous analyses, potentially indicating the broader clinical relevance of BRCA1/2 genetic testing. jamanetwork.com/journals/jamaoncology/fullarticle/2791277
Treatment with sacituzumab tirumotecan significantly improved progression-free survival (PFS) and overall survival (OS) when compared to chemotherapy for patients with heavily pretreated, advanced triple-negative breast cancer, according to phase 3 data presented at the 2024 ASCO Annual Meeting. The antibody-drug conjugate sacituzumab tirumotecan targets TROP2, which is overexpressed in triple-negative breast cancer and often correlates with adverse outcomes. In a phase 3 study, researchers assigned 263 patients with advanced triple-negative breast cancer to monotherapy with sacituzumab tirumotecan (n = 130) or to physician’s choice chemotherapy (n = 133). The median age of the study cohort was 51 years, and the heavily pretreated population had received two or more previous therapies, including at least one therapy in the metastatic setting. In total, prior PD-1/PD-L1 inhibitors receipt was 26%, and 48% had received three or more lines of prior chemotherapy in the advanced setting. The rate of visceral metastases was 87%. PFS served as the primary endpoint. Results of an interim analysis revealed that assignment to sacituzumab tirumotecan correlated with a 69% reduction in the risk of progression or death (hazard ratio [HR] = 0.31; 95% CI, 0.22-0.45; P < .00001). The median PFS for patients assigned to sacituzumab tirumotecan was 5.7 months (95% CI, 4.3-7.2), compared to 2.3 months (95% CI, 1.6-2.7) for patients assigned to chemotherapy. The 6-month PFS rates were 43.4% and 11.1%, respectively. Among patients with a TROP2 H-score above 200, the median PFS with sacituzumab tirumotecan was 5.8 months, compared to 1.9 months for chemotherapy (HR = 0.28; 95% CI, 0.17-0.48). Median follow-up for OS was 10.4 months. The researchers observed a significant trend toward improved OS for patients assigned to sacituzumab tirumotecan (median, not reached vs 9.4 months; HR = 0.53; 95% CI, 0.36-0.78; P = .0005). The objective response rate also favored sacituzumab tirumotecan (43.8% vs 12.8%). Treatment with sacituzumab tirumotecan was well tolerated. The most common treatment-related adverse events (grade 3 or higher) included decreased neutrophil count (sacituzumab tirumotecan vs chemotherapy, 32.3% vs 47%), anemia (27.7% vs 6.1%), and decreased white blood cell count (25.4% vs 36.4%).
I am looking forward to turning 75 in a few years because I have dense breasts, and it seems to me that when in doubt, even with no symptoms, I always get recommended for unnecessary 6 month mammograms and/or unnecessary painful biopsies. At 75, I shall tell my doctor, no thanks, I'm done with this....and celebrate!!
A recent retrospective study from Seoul National University showed adjuvant endocrine therapy for low ER expression (1-10%) may not improve survival unless patients had no adjuvant radiation therapy. The study included both pre-and post menopausal women and both tamoxifen and AIs. www.researchsquare.com/article/rs-2013852/v1
ESMO 2023 Congress Abstract by MD Anderson Cancer Center reported an interesting finding: no surgery necessary after neoadjuvant therapy including radiation therapy for patients with T-2 N0-1 triple negative or HER2+ early breast cancer: Abstract 243MO Background Neoadjuvant systemic therapy (NST) for triple-negative breast cancer (TNBC) and HER2+ breast cancer (HER2+BC) yields a pathol-ogic complete response (pCR) in approximately 60% of patients. A pCR to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). Radiotherapy alone, without breast surgery after NST among patients who had a VACB-determined pCR was evaluated in the feasibility phase (Johnson et al. JACS 2023 ), 2-year pre-planned primary outcome (Kuerer et al Lancet Onc 2022 ), the 32.4 mo patient reported outcomes (Johnson et al SSO 2023 ) and now at the preplanned 3-year primary endpoint. Methods This multicentre phase II clinical trial enrolled women aged ≥40 years with unicentric cT1-2N0-1M0 TNBC or HER2+BC and a residual breast lesion
On March 3, 2023, the FDA approved abemaciclib with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence. Patients defined as high risk included those having either ≥4 pALN (pathologic axillary lymph nodes) or 1-3 pALN and either tumor grade 3 or a tumor size ≥50 mm. Abemaciclib was previously approved for the above high-risk population with the additional requirement of having a Ki-67 score ≥20%. FDA removed the Ki-67 testing requirement.
Monarch E trial: the latest (5-yr follow up) report: The combination of adjuvant abemaciclib plus endocrine therapy significantly reduced the risk of long-term recurrence and improved invasive disease-free survival (DFS) for patients with HR-positive, HER2-negative, high-risk early breast cancer, according to a 5-year efficacy analysis of the monarchE study presented at ESMO Congress 2023. The high risk factors were described in the lecture above.
The FDA approved olaparib as an adjuvant treatment in patients with deleterious or suspected deleterious germline BRCA mutated HER2-negative high-risk early breast cancer who were pretreated with neoadjuvant or adjuvant chemotherapy, according to a press release. Olaparib is a PARP inhibitor. The recommended dose of olaparib is 300 mg orally twice daily for up to one year. This approval was based on results from the OlympiA trial of 1,836 patients with gBRCA mutated HER2-negative high-risk early breast cancer. The primary efficacy endpoint was invasive disease-free survival. After 3 years, invasive disease-free survival for patients receiving olaparib was 86% and just 77% for patients on placebo. When looking at overall survival, there were 75 deaths in the olaparib arm compared to 109 deaths in the placebo arm.
October 2023: Despite the proven benefit of adding an immune checkpoint inhibitor (ICI) to preoperative chemotherapy for patients with triple-negative breast cancer (TNBC), for example, pembrolizumab, the NeoTRIP Michelangelo trial using atezolizumab stumbled at the finish line, showing that adding atezolizumab (Tecentriq) to nab-paclitaxel and carboplatin followed by surgery and adjuvant anthracycline-based chemotherapy did not improve 5-year event-free survival (EFS), compared with the same regimen without atezolizumab.
The FDA approved olaparib for the treatment of patients with high-risk HER2- early breast cancer and germline BRCA mutations in March 2022 based on OlympiA trial. Patients had neo- or adjuvant chemotherapy followed by Olaparib for 1 year as an adjuvant therapy, which was published in NEJM. www.nejm.org/doi/full/10.1056/NEJMoa2105215 Compared with placebo, treatment with olaparib led to a 42% reduction in the risk for invasive breast cancer recurrence, new cancer, or death (HR = 0.58; 95% CI, 0.41-0.82; P < .0001). Now, the European Medicines Agency’s Committee for Medicinal Products in Human Use recommended the approval of olaparib as an adjuvant treatment for patients with high-risk HER2-negative early breast cancer with germline BRCA mutations in August 2022.
New Breast Cancer Screening Guideline by USPSTF May 10,2023 USPSTF proposed reducing the recommended start age for routine screening mammograms from age 50 to age 40. The latest recommendation, which carries a B grade, also calls for screening every other year and sets a cutoff age of 74. The task force's A and B ratings indicate strong confidence in the evidence for benefit, meaning that clinicians should encourage their patients to get these services as appropriate. The influential federal advisory panel last updated these recommendations in 2016. At the time, USPSTF recommended routine screening mammograms starting at age 50, and gave a C grade to starting before that.
I mentioned the EMERALD trial showing improved DFS with elacestrant, a new SERD. Now, elacestrant was approved by FDA on 1/27/2023 for post menopausal metastatic HR(+) HER2(-) and ESR1 mutation(+) breast cancer progressed over at least 1 endocrine therapy. ESR mutation can be tested by Guardant 360 CDX test. It’s based on EMERALD trial. ascopubs.org/doi/full/10.1200/JCO.22.00338
In June 2022 American Society of Clinical Oncology (ASCO) Annual Meeting: PALOMA 2 trial final report: Palbociclib (Ibrance) + lettozole was not better than letrozole alone in overall survival. It is a surprising news as ribociclib showed survival benefit.
New approval for metastatic ER+ HER2- breast cancer in November 2023. The US Food and Drug Administration (FDA) has approved capivasertib (Truqap, AstraZeneca Pharmaceuticals) with fulvestrant for certain previously treated adults with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative, locally advanced or metastatic breast cancer. Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement. The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib. Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor-based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy. Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity. In the 289 patients with PIK3CA/AKT1/PTEN-altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months vs 3.1 months in the placebo group (hazard ratio [HR], 0.50). An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN-alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% CI, 0.61-1.02), indicating that "the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN-alteration," the FDA explained. Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis. The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.
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I would like to clarify RxPonder Trial by SWOG: In ER+ HER2- LN1-3 + early breast cancer and Oncotype DX RE 0-25: Post menopausal women: endocrine Tx alone (no benefit by adding chemotherapy. However, premenopausal women need endocrine and chemotherapy as the combination of endocrine and chemotherapy improved DFS.
Dr Kim… if stage 1b TNBC / lesion 8mmx4mm found ~ in rt breast ~ on routine mammogram ~ had neoadjunctice TC CHEMO prior to double Mastectomy ( profilactic ) NEG Sentinal nodes and Lymph nodes on surgical pathology report… no suspicious nodes found prior to treatment with complete tumor response to chemo….QUESTION: Sentinal Node and Lymph node biopsy ( blue dye) was done ONLY after neoadjunctive chemo… could micro seedlings of cancer cells in nodes even have been determined in said nodes if they were already dead from prior chemo therapy ⁉️⁉️ ⁉️⁉️⁉️ neoadjuctive therapy; would microseedlings to
For metastatic HER2 (+) breast cancer, the first line treatment is THP (Taxotere, Herceptin , Perjeta) which provides objective response rate of 80% and overall survival almost 5 years. Now, Destiny-Breast 03 trial report shows Enhertu (trastuzumab emtansine) was superior to Kadcyla (trastuzumab deruxtecan). But there is no randomized study directly comparing THP with Enhertu (trastuzumab emtansine). The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended trastuzumab deruxtecan for approval in the treatment of adults who have unresectable or metastatic HER-2 positive breast cancer in the European Union. “This recommendation reflects the transformative progression-free survival benefit seen in the DESTINY-Breast03 trial compared to Enhertu (trastuzumab emtansine) supporting Kadcyla (trastuzumab deruxtecan) as a potential new standard of care and setting a new benchmark in the treatment of HER2-positive metastatic breast cancer. In the phase 3, randomized DESTINY-Breast03 trial, researchers reported that 75.8% (95% CI, 69.8-80.7) of patients assigned to trastuzumab deruxtecan were alive without disease progression at 1 year, compared with just 34.1% (95% CI, 27.7 to 40.5) of those assigned to trastuzumab emtansine, meaning those assigned to the former were at a 72% reduced risk for death (HR = 0.28; 95% CI, 0.22-0.37; P < .0001). Furthermore, the researchers continued, 94.1% (95% CI, 90.3 to 96.4) of patients assigned to trastuzumab deruxtecan were alive at 1 year, compared with 85.9% (95% CI, 80.9 to 89.7) among those assigned to trastuzumab emtansine.
Stereotactic ablative body radiotherapy (SABR) for Oligometastasis Stereotactic ablative body radiotherapy (SABR) appeared to delay the need for changes in systemic therapy in postmenopausal patients with oligoprogressive luminal ER-positive, HER2-negative breast cancer, according to a new phase 2 study. In the AVATAR trial, patients with one to five metastatic lesions who’d been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and aromatase inhibitors for at least 6 months underwent SABR. Of those, 47% had event-free survival of more than 6 months. Participants could not have had leptomeningeal disease, previous chemotherapy for metastatic disease, or prior radiotherapy to an oligoprogressing lesion. Most metastases were to bone (n = 44, 71%), node (systemic, n = 8; 13%) and lung (n = 4; 6%). The patients were treated with SABR, most commonly 24 Gy (n = 25; 43%) and 20 Gy (n = 10; 17%); half had one lesion treated (50%), and 25% had two lesions treated. The median follow-up was 15.8 months. The median event-free survival was 5.2 months (95% confidence interval, 3.1-9.4 months), with events defined as progression within 6 months or in at least three lesions. Fifteen patients (47%) reached event-free survival of 6 or more months. Median modified progression-free survival was 10.4 months, and median progression-free survival was 5.2 months; 31% of patients received SABR for further oligoprogression, and 46% patients remained on CDK4/6 inhibitors and aromatase inhibitors for 12 months. Overall survival was 100%. A total of 14 patients had grade 1 adverse events, 2 had grade 2 events, and none had grade 3 or higher events; 47% had no treatment-related toxicity. However, further randomized trials are required before routine implementation in clinical practice. For now, patients should be considered in a case by case basis with multidisciplinary discussion to determine the optimal systemic therapy regimen at oligoprogression and whether SABR may provide benefit.
Sacituzumab govitecan is approved by FDA for metastatic triple negative breast cancer. A recent study (TROPiCS-02) showed it may be effective for ER + metastatic breast cancer. The first analysis of the phase 3 TROPiCS-02 study, showed that patients on sacituzumab govitecan had a median progression-free survival of 5.5 months compared to 4 months for patients on physician choice chemotherapy. At 12 months, 21% of patients were free of disease progression and alive in the sacituzumab arm compared to 7% of patients in the chemotherapy arm. meetings.asco.org/abstracts-presentations/206927
SG (vs TPC) improved median PFS (5.5 vs 4.0 mo; HR, 0.66; 95% CI, 0.53-0.83; P= 0.0003); PFS rates at 6 and 12 mo were 46% vs 30% and 21% vs 7%, respectively. SG vs TPC showed a numeric but nonsignificant difference in OS (13.9 vs 12.3 mo; HR, 0.84; P= 0.143); ORR (21% vs 14%) and clinical benefit rate (34% vs 22%) were higher with SG vs TPC and median duration of response was 7.4 vs 5.6 mo, respectively. Overall, 74% vs 60% of patients (SG vs TPC) had grade ≥3 treatment-emergent adverse events (AEs); neutropenia (51% vs 39%) and diarrhea (10% vs 1%) were most common. AEs leading to discontinuation of SG vs TPC were low (6% vs 4%).
The choice of fulvestrant as endocrine therapy did not significantly improve overall survival (OS) compared to anastrozole among postmenopausal patients with HR-positive advanced breast cancer who were naive to endocrine therapy. According to the final analysis of the FALCON study presented at ESMO Congress 2023. However, for non-visceral metastatic disease, fulvestrant showed better overall survival than anastrazole which was not statistically significant. www.annalsofoncology.org/article/S0923-7534(23)01397-2/fulltext
Please HELP!!! I'm 72 years old with neuroendoccrine breast carcinoma 3.1cm stage 2 poorly differentiated. I'm aware its a very agressive cancer. I had lumpectomy and my surgeon confirms that lymphs nodes were negative er+ pr+ her2- . All tissue around cancer margins very good. I saw two oncologists, one for radiation and the other for chemo. They don't know if I will benefit from chemo but I will have radiaton and hormones therapy. What kind of treatment do you think I should have and what are prognostic for this kind of cancer if I take chemo??? I'm in a good health but I want to have quality of life too and if treatment won't help to live longer then I would refuse chemo treatment. COULD IT BE A PRIMARY CANCER IF THEY DON'T SEE ANYTHING ON SCANS like nuclear bone, ct scan for abdo chest and brain???
It’s a very rare cancer that no oncologist can say confidently about how to treat. So we follow the general rule of common breast cancer therapy. With no lymph node metastasis and relatively small size tumor which was resected completely, I would say it is fortunate. Please have your oncologist check for the ki-67 index of the cancer. If is over 10%, chemotherapy may help. The high ki-67 index means more aggressive cancer which responds to chemotherapy. Age didn’t matter, many elderly patients tolerate it well especially otherwise healthy people like you. Because of + ER, endocrine therapy is important. God luck and God bless you!
Thank you for your response. At the beginning my oncologist admitted he didn't know how to treat me. He phone me and says he wants me to do 4 rounds of strong chemo and then 12 less strong treatment. Then its 3 weeks radiation and 1 week booster. He told me that if i don't take treatments I have 80% chance of reccurence. When i do research the rate for survival between chemo and no treatments is not much. I don't know what to do. Is it worth it having to deal with all the side effects!!!
An interesting article was just published in the American Cancer Society journal regarding higher stages of ER+ HER2- Invasive lobular carcinoma (ILC) requiring chemotherapy: Neoadjuvant or adjuvant chemotherapy did not improve cancer specific and overall survival (as long as they have endocrine therapy). In other words, patients with ER+, HER2-, ILC who will have endocrine therapy may not need neo- adjuvant chemotherapy. However, this result has to be confirmed before considering the standard of care. acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35125
KEYNOTE-355 Update Report: In November 2020 FDA approved pembrolizumab in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥10). It was based on improved progression free survival not based on the overall survival data. Now the updated report was published confirming the benefit of pembrolizumab+chemotherapy in improving overall survival. www.nejm.org/doi/full/10.1056/NEJMoa2202809
The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren't effective or can't be tolerated. It's also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. This new warning updates a November 2022 alert based on preliminary evidence for a "substantial risk" for hypocalcemia in patients with CKD on dialysis.
Finally the result of MonarchE trial with the 5 year follow up was presented in 2023 ESMO. Results of a planned 5-year efficacy analysis of the monarchE trial showed that at a median follow-up of 4.5 years, the abemaciclib/endocrine therapy combination was associated with a 7.6% absolute improvement in invasive disease-free survival (IDFS) and 6.7% edge in distant relapse-free survival (DRFS), compared with endocrine therapy alone The monarchE trial included two cohorts: a primary cohort consisting of patients deemed at high risk based on clinical pathological features such as the number of involved axillary nodes, grade 3 disease, and tumors 5 cm or larger, and a second cohort of patients with lower disease grade and smaller tumors but with high levels of the proliferation marker Ki-67. A total of 5,637 patients were randomized to receive either 2 years of abemaciclib 150 mg twice daily plus endocrine therapy, or endocrine therapy alone, followed by 3-8 years of additional endocrine as clinically indicated in each study arm. An earlier preplanned interim analysis of the phase 3 trial of more than 5,600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology. As that analysis showed, at a median follow-up of 15.5 months abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of IDFS vs. endocrine therapy alone. The IDFS benefit with the combination was consistent across most subgroups, including older patients, perimenopausal and postmenopausal patients, those who had received prior neoadjuvant or adjuvant chemotherapy, all tumor sizes, number of positive lymph nodes, less favorable tumor stage or grade, and order of endocrine therapy (tamoxifen or aromatase inhibitor as first drug). As noted before, DRFS, a secondary endpoint, also favored abemaciclib, with 345 events occurring over 5 years in the combination arm, compared with 501 in the endocrine therapy arm alone. This translated into a HR with the combination of 0.68 (P < .001). The proportions of patients with treatment-emergent adverse events and serious adverse events (SAEs) were higher in the combination arm than in the endocrine therapy alone arm in all previous analyses of the trial data. The NATALEE trial, in which patients were randomized to endocrine therapy with or without the CDK4/6 inhibitor ribociclib (Kisqali) was previously shown to provide a significant survival advantage for women with both high-risk and intermediate-risk patients with early breast cancer: the absolute difference in 3-year IDFS rates between the combination group and endocrine monotherapy groups was 3.3%. To determine the ultimate value of combining a CDK4/6 inhibitor with endocrine therapy in early breast cancer, longer follow-up of both trials will be necessary. Questions that still need to be answered include the optimal duration of CDK4/6 inhibitor therapy, whether adjuvant therapy should be resumed when there are signs of renewed proliferation, and whether there would be a benefit to restarting CDK4/6 inhibitors when metastasis occurs.
Triple negative breast cancer stage 1 may not need neoadjuvant or adjuvant chemotherapy if stromal tumor infiltrating lymphocytes (TIL) are over 50%. jamanetwork.com/journals/jamaoncology/article-abstract/2820527
After neoadjuvant therapy for early HER2 (+) breast cancer, breast conservation therapy provides better overall survival than mastectomy among patients who achieved pathological complete response (pCR) in the axillary lymph nodes. But among patients with pCR in the breast, the survival did not differ. www.thelancet.com/journals/lanam/article/PIIS2667-193X(24)00039-5/fulltext#%20
In postmenopausal women treated for early-stage estrogen receptor-positive breast cancer, neither Vaginal estrogen therapy (VET) nor MHT (menopausal hormone therapy) was associated with increased risk of recurrence or mortality. A subgroup analysis revealed an increased risk of recurrence, but not mortality, in patients receiving VET with adjuvant aromatase inhibitors. academic.oup.com/jnci/article/114/10/1347/6645744?login=false
However, a subgroup analysis revealed an increased risk of recurrence, but not mortality, in patients receiving VET with adjuvant aromatase inhibitors (but not with tamoxifen).
Partial breast irradiation is recommended over whole breast irradiation for ‘’node negative ER + early breast cancer. The American Society for Radiation Oncology (ASTRO) has issued an updated clinical practice guideline on partial breast irradiation for women with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). The 2023 guideline, which replaces the 2017 recommendations, factors in new clinical trial data that consistently show no significant differences in overall survival, cancer-free survival, and recurrence in the same breast among patients who receive partial breast irradiation compared with whole breast irradiation. The data also indicate similar or improved side effects with partial vs whole breast irradiation. For patients with early-stage, node-negative invasive breast cancer, the updated guideline strongly recommends partial breast irradiation instead of whole breast irradiation if the patient has favorable clinical features and tumor characteristics, including grade 1 or 2 disease, estrogen receptor (ER)-positive status, small tumor size, and age 40 or older. The updated guideline also conditionally recommends partial over whole breast irradiation if the patient has risk factors that indicate a higher likelihood of recurrence, such as grade 3 disease, ER-negative histology, or larger tumor size. The task force does not recommend partial breast irradiation for patients with positive lymph nodes, positive surgical margins, or germline BRCA1/2 mutations or patients under 40. Given the lack of robust data in patients with less favorable risk features, such as lymphovascular invasion or lobular histology, partial breast irradiation is conditionally not recommended for these patients. For DCIS, the updated recommendations mirror those for early-stage breast cancer, with partial breast irradiation strongly recommended as an alternative to whole breast irradiation among patients with favorable clinical and tumor features, such as grade 1 or 2 disease and ER-positive status. Partial breast irradiation is conditionally recommended for higher grade disease or larger tumors, and not recommended for patients with positive surgical margins, BRCA mutations or those younger than 40. Recommended partial breast irradiation techniques include 3-D conformal radiation therapy, intensity modulated radiation therapy, and multicatheter interstitial brachytherapy, given the evidence showing similar long-term rates of ipsilateral breast recurrence compared with whole breast irradiation. Single-entry catheter brachytherapy is conditionally recommended, and intraoperative radiation therapy techniques are not recommended unless integrated into a prospective clinical trial or multi-institutional registry. The guideline also outlines optimal dose, fractionation, target volume, and treatment modality with different partial breast irradiation techniques, taking toxicities and cosmesis into consideration.
Atezolizumab didn’t help to improve pathological complete response rate for HER (+) high risk breast cancer when added to classical dose dense AC-T in a neoadjuvant setting. ascopubs.org/doi/full/10.1200/JCO.21.02772?bid=183384593&cid=DM10951 So far,
Breast conservation therapy is feasible for ipsilateral multiple breast cancer: local recurrence about 3% in 5 years, not different from single tumor. ascopubs.org/doi/abs/10.1200/JCO.22.02553?journalCode=jco
Exemestane + ovarian suppression is better than tamoxifen + ovarian suppression or tamoxifen alone in premenopausal ER+ HER2- early invasive lobular breast cancer www.medscape.com/viewarticle/exemestane-plus-ovarian-suppression-best-early-invasive-2024a10009tv However, it is not clear if patients with invasive ductal breast cancer can have de-escalated therapy such as tamoxifen alone.
Neoadjuvant therapy for TNBC with carboplatin, Docetaxel and pembrolizumab jamanetwork.com/journals/jamaoncology/article-abstract/2812294 The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.5 This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m2), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC. The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%).
An interesting study of adjuvant endocrine therapy for hormone receptor (+) premenopausal patients: 2 years of goserelin (Zoladex: GnRH agonist) alone is good enough for genomic high risk group over combination of goserelin + tamoxifen. The combination caused more side effects and intersection without benefit. Tamoxifen alone benefits genomically low risk group. ascopubs.org/doi/full/10.1200/JCO.21.02844?bid=188486727&cid=DM11130
8 years of follow up after neratinib (HER2 TK inhibitor) adjuvant therapy, overall survival was not different from placebo group. Although neratinib improved invasive disease free survival, it did not improve overall survival. www.ejcancer.com/article/S0959-8049(23)00063-1/fulltext#:~:text=Eight%2Dyear%20overall%20survival%20rates,1.21%3B%20p%20%3D%200.6914).
PET-CT Scanning Improves Detection of Metastases in Patients With Locally Advanced Breast Cancer (Stage llB; T3N0 - Stage lll) ascopubs.org/doi/full/10.1200/JCO.23.00249?journalCode=jco Data suggest that whole-body PET-CT scanning may act as a superior method for detecting distant metastases and identifying patients who would benefit from less aggressive therapy. The researchers randomly assigned patients to whole-body 18F-labeled fluorodeoxyglucose PET-CT scanning or conventional staging methods. Upstaging to stage IV metastatic disease served as the study’s primary endpoint. Receipt of multimodal therapy served as a key secondary endpoint. The study included data from 369 patients (PET-CT, n = 184; conventional staging, n = 185). A significantly higher percentage of patients assigned to PET-CT scanning were upstaged to stage IV than patients assigned to conventional staging (23% vs. 11%; relative risk, 2.4; 95% CI, 1.4-4.2; P = .002). In the PET-CT arm, the most common sites for distant metastases among upstaged patients included bone (alone, = 14; plus another site, n = 15), mediastinal nodes (alone, n = 3; plus other site, n = 11), liver (alone, n = 2; plus another site, n = 4), and lung (alone, n = 3; plus another site, n = 7). Bone was the most common site of metastases in the conventional staging arm (alone, n = 6; plus another site, n = 8). Although the researchers did not consider cancer detection in regional nodes a basis for upstaging, they noted that a significantly higher percentage of upstaged patients in the PET-CT arm had positive regional nodes compared to upstaged patients in the conventional staging arm (97.7% vs. 61.9%; P = .03). In total, 81.3% of upstaged PET-CT patients (n = 35 of 43) and 95.2% of upstaged conventional staging patients (n = 20 of 21) had their intended treatment platform changed. Nineteen percent of patients assigned to PET-CT scanning did not receive combined modality treatment, compared to 11% of patients assigned to conventional staging (absolute difference, 8.2%; 95% CI, 0.1-15.4; P = .03).
PostMONARCH trial: abemaciclib + fulvestrant is better than placebo + fulvestrant for ER + HER2- metastatic breast cancer progressed over previous CDK4/6 inhibitor plus endocrine therapy. ORR16%, PFS at 6 Mon. 50%. www.medscape.com/s/viewarticle/abemaciclib-combo-improves-survival-advanced-breast-cancer-2024a1000anu?ecd=WNL_clinicdgst_240731_MSCPPERSO_6712876_pos1&uac=289993FT&impID=6712876&form=fpf
No OS Benefit with Margetuximab Over Trastuzumab in Previously Treated HER2+ Breast Cancer Final overall survival results from the phase 3 SOPHIA trial revealed that the progression-free survival advantage seen with margetuximab over trastuzumab in an earlier analysis did not translate into a significant OS benefit in patients with previously treated HER2-positive metastatic breast cancer. The earlier PFS analysis of the study led to FDA approval of margetuximab with chemotherapy in patients with HER2-positive metastatic breast cancer who have received at least 2 prior anti-HER2 regimens-at least one of which was for metastatic disease. A total of 536 patients in the intention-to-treat population were randomly assigned to treatment with either IV margetuximab (15 mg/kg once every 3 weeks; n = 266) plus chemotherapy or IV trastuzumab (6 mg/kg once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. The final OS analysis was triggered by a total of 385 deaths, which had occurred at a median follow-up of 20.2 months. At that point, it was found that median OS was 21.6 months among patients treated with margetuximab, compared with 21.9 months among their counterparts treated with trastuzumab. The researchers also performed a pre-planned subgroup analyses of OS by type of chemotherapy and HER2 status, which showed no difference in survival between margetuximab and trastuzumab. On the other hand, an exploratory analysis of CD16A genotyping suggested a possible OS improvement among CD16A-158FF patients treated with margetuximab (median 23.6 months) relative to trastuzumab (median 19.2 months; HR = 0.72; 95% CI, 0.5-1). Similar analyses revealed a possible OS benefit for trastuzumab in CD16A-158VV patients relative to margetuximab (median OS 31.1 vs 22 months; HR = 1.77; 95% CI, 1-3.1). Safety analyses found that margetuximab was comparable with trastuzumab. Treatment discontinuation due to adverse events were observed in 4% of patients in each treatment group. In light of these findings, the investigators wrote that the PFS advantage previously observed with margetuximab-chemotherapy did not translate into a significant difference in OS in the intention-to-treat population of the SOPHIA trial. They added that further studies of margetuximab in patients with HER2+ breast cancer with different CD16A allelic variants are warranted.
“My help comes from the Lord.” Thank you Doctor for this presentation and for your care of breast cancer patients.💕God Bless!
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Dr. Kim, thank you so much for this excellent presentation and your updates. I’m a new NP in the field of cancer and this is the first time information regarding BC is making sense. I saved you videos and keep checking them for updates. Is it safe to assume that you will keep platin updates as they become available - under the comments section? Please please do not give up on your page! You are the first person who made tremendous difference on my learning because your videos are so informative. God bless you and your work!!!
I work with NPs and PAs at hospitals.
I am happy that my lecture helps you treat your patients.
Praveen pppp
Thank you, Dr. Kim, so much.
Thank you Dr. Kim. I see all your videos.
I mentioned that breast cancer screening is a controversial issue.
Now NCCN threw another controversy:
The new NCCN guidelines state that women should undergo a breast cancer risk assessment starting at age 25 years, and they emphasize annual mammography screening beginning at age 40 years for those with average risk.
The new NCCN guideline also states that earlier start may be recommended for those with additional risk factors, and screening is also important for those who are pregnant or breastfeeding.
Thank you very much, sir!
In March 2022, olaparib was approved by FDA for adjuvant treatment for patients with high-risk HER 2(-) early breast cancer and germline BRCA mutations.
Now in July 2022, it was recommended by The European Medicines Agency’s Committee for Medicinal Products in Human Use.
The FDA has approved trastuzumab deruxtecan (Enhertu) for the treatment of patients with unresectable or metastatic HER2-low breast cancer on August 5, 2022.
This is the first therapy approved for HER2-low breast cancer, a newly defined subset of HER2-negative breast cancer in which there are some HER2 proteins on the cell surface, but not enough to warrant classification as HER2-positive cancer.
The indication is for patients who have received prior chemotherapy in the metastatic setting or for patients whose cancer has returned during adjuvant chemotherapy or within 6 months of completing it.
This approval is based on DESTINY-Breast04, a randomized, multicenter, open label clinical trial that enrolled 557 adult patients with unresectable or metastatic HER2-low breast cancer. The trial included two cohorts: 494 hormone receptor positive (HR+) patients and 63 hormone receptor negative (HR-) patients. Of these patients, 373 randomly received Enhertu by intravenous infusion every three weeks and 184 randomly received physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel or paclitaxel). The results showed improvement in both progression-free survival and overall survival in people with unresectable or metastatic HER2-low breast cancer.
The median age of trial participants was 57 years old, ranging from 28 to 81 years of age. Among the 557 patients, 24% were age 65 or older. Females comprised 99.6% of the trial population. Trial participants’ race was reported as 48% White, 40% Asian, 2% Black or African American, and 3.8% Hispanic/Latino.
The most common adverse reactions in patients receiving Enhertu in DESTINY-Breast04 are nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain and diarrhea. The prescribing information includes a boxed warning to advise health care professionals of the risk of interstitial lung disease and embryo-fetal toxicity. Enhertu is not recommended for women who are pregnant.
Trastuzumab Deruxtecan Improves PFS in Patients with HER2-Low Metastatic Breast Cancer (after progression over previous endocrine therapy): Destiny Breast06 study
meetings.asco.org/abstracts-presentations/238015
NCCN guidelines include fluoroestradiol F18 (FES) PET scan for evaluation of ER positive recurrent or metastatic breast cancer in August 2023.
However, this imaging study has been approved in 2020 by FDA.
I also described fluoroestradiol F18 (FES) PET scan in the presentation.
Thank you sir your lecture helped understand the process of investigation
You’re welcome
Axillary lymph node dissection is NOT necessary for 1 or 2 sentinel lymph nodes positive early breast cancer (NCCN and ASCO guidelines):
The ACOSOG Z0011 Trial (JAMA 2017 Sep 12;318):
Among patients with T1 or T2 (< 5cm), 1 or 2 Sentinel LNs containing metastases, 10-Vr
overall survival was not inferior for patients who had Sentinel LN Biopsy alone when
compared with those who underwent axillary LN dissection (AND) after Sentinel LN
Biopsy.
• This study included both pre-and post-menopausal women.
• This study only included patients who had breast conservation therapy (lumpectomy +
radiation therapy).
Therefore, patients who had mastectomy still need ALND for (+) axillary LNs metastases
However, the AMAROS Trial revealed that axillary radiation was as effective as AND in
regional recurrence and overall survival rates at 10-yrs, but with less lymphedema (15%
vs 30%)- presented at San Antonio Breast Cancer Symposium 12/2018.
New subscriber!
I mentioned earlier that sacituzumab gavitecan was approved by FDA for triple (-) metastatic breast cancer. I also mentioned that TROPiCS-02 trial result showed improved DFS (and OS).
Now, On February 3, 2023, the FDA approved sacituzumab govitecan-hziy (Trodelvy) for patients with unresectable locally advanced or metastatic HR(+) HER-2(-) breast cancer who have received endocrine-based therapy and at least two additional systemic therapy including one chemotherapy.
It’s based on TROPiCS-2 trial:
ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA1001
TROPiCS-02 took patients who had received two to four prior lines of chemotherapy for metastatic hormone receptor-positive breast cancer and randomized them to get sacituzumab or to get treatment of physician's choice of chemotherapy. The study found that the patients receiving sacituzumab had a longer progression-free survival, longer overall survival, and a higher response rate. This really means for patients who've had prior endocrine therapy and a CDK4/6 inhibitor, and at least one prior chemotherapy regimen for their metastatic disease, this is now a new standard therapy option.
Sacituzumab is administered weekly IV: 2 weeks in a row and then a week off.
Side effects: hair loss; usually mild diarrhea, and neutropenia.
Fulvestrant vs. anastrazole for metastatic ER+ HER2- breast cancer:
The choice of fulvestrant as endocrine therapy did not significantly improve overall survival (OS) compared to anastrozole among postmenopausal patients with HR-positive advanced breast cancer who were naive to endocrine therapy, according to the final analysis of the FALCON study presented at ESMO Congress 2023.
The initial analysis of FALCON met its primary endpoint by showing a statistically significant improvement in progression-free survival for patients assigned to fulvestrant rather than anastrozole. However, the improvement was limited to patients with non-visceral disease (hazard ratio [HR] = 0.59; 95% CI, 0.42-0.84).
The study included data from 462 patients with locally advanced or metastatic breast cancer. Among the full cohort, patients assigned to fulvestrant had a median OS of 44.8 months compared with 42.7 months for patients assigned to anastrozole.
Among patients with non-visceral disease, assignment to fulvestrant correlated with a 15% reduction in the risk of death (median, 65.2 months vs 47.8 months). However, the difference did not reach statistical significance (HR = 0.85; 95% CI, 0.6-1.2). For patients with visceral disease, there was no significant improvement in OS associated with fulvestrant (median, 37.2 months vs 40.7 months).
The combination of palbociclib and fulvestrant did not prolong progression-free survival compared to fulvestrant alone in patients with hormone receptor-positive/HER2-negative metastatic breast cancer who had disease progression on prior treatment with a CDK4/6 inhibitor and endocrine therapy, according to findings from the PACE study presented at the 2022 San Antonio Breast Cancer Symposium.1 However, the study also showed that the triplet combination of the PD-L1 inhibitor avelumab with palbociclib and fulvestrant arm led to a doubling in progression-free survival.
In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.
Using the Oncotype DX Breast DCIS Score test, a laboratory test that estimates DCIS recurrence risk, may help identify patients with low-risk DCIS who can safely avoid adjuvant radiation after surgery, according to new research (abstract GS03-01) presented on December 8 at the 2023 San Antonio Breast Cancer Symposium.
Researchers found that the Oncotype DX score helped identify patients who are at low and high risk for DCIS recurrence. Low-risk patients who skipped adjuvant radiotherapy after breast-conserving surgery demonstrated similar 5-year recurrence rates compared with high-risk patients who received adjuvant radiotherapy.
However, to be accepted as the standard of care, it needs larger and better trials as well as longer follow-up to confirm this less-is-more approach.
New drug for metastatic breast cancer:
On 1/27/23, FDA approved elacestrant (Orserdu) for postmenopausal women or men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer that progressed on at least one line of endocrine therapy including CDK4/6 inhibitors. When compared with fulvestrant or aromatase inhibitors, it improved progression free survival by 2 months (3.8 vs. 1.9 months).
Dose: 345 mg by mouth a day
Side effects: hyper cholesterol and triglycerides; musculoskeletal pain, liver dysfunction (for moderate liver disease, dose needs to be reduced)
ESR1 receptor mutation is tested by Guardant360 CDX.
Capivasertib + endocrine therapy was recently approved for Horome Receptor + HER2- metastatic breast cancer which has + AKT1 or PIK3CA mutation as a second line therapy.
ASCO issued a rapid recommendation update, published in the Journal of Clinical Oncology, regarding the use and timing of endocrine and targeted therapies for patients with HR-positive, HER2-negative metastatic breast cancer. The updated recommendations build upon clinical practice guidelines originally published in July 2021.
This update was based on results from the CAPItello-291 study, a phase 3 clinical trial evaluating fulvestrant plus capivasertib in patients with metastatic breast cancer. Capivasertib is an AKT pathway inhibitor, and the study included patients with AKT1, PIK3CA, and PTEN alterations. Following results of the study, the FDA approved capivasertib, along with a companion diagnostic, in November 2023.
The panel recommended that patients with HR-positive, HER2-negative breast cancer should receive multiple lines of endocrine therapy, usually in combination with targeted therapies. Genomic testing for activating mutations should be regularly performed. CDK4/6 inhibitors should be paired with endocrine therapy in the first line, while second- and third-line therapy should be determined through genomic testing.
Capivasertib plus endocrine therapy was recommended for patients whose tumors harbor PIK3CA or AKT1 mutations or PTEN inactivation. Patients with PIK3CA mutations can be considered for treatment with alpelisib, but patients with AKT1 mutations should not be.
“There are no comparative efficacy data for choosing a PIK3CA targeted option for those who are potential candidates for capivasertib or alpelisib treatment,” the panelists wrote. “For such patients, the panel recommends selecting the targeted agent based on perceived risk-benefit considerations such as hyperglycemia, diarrhea, or treatment discontinuation for adverse events.”
The panel noted that grade 3 diarrhea and rash occurred more commonly with capivasertib (9.3% vs 6.7% and 12.1% vs 9.9%, respectively) but that hyperglycemia was more common among patients treated with alpelisib (36.6% vs 2.3%). Antihistamines, anti-diarrheal agents, and supportive care measures can be employed to mitigate potential symptoms caused by these adverse events.
Everolimus can be considered for all patients regardless of tumor genomics. Monotherapy with elacestrant can be considered for patients with tumors harboring an ESR1 mutation.
“While newer agents have been added to the armamentarium, there remain few studies on the optimal timing or sequence of treatments, comparisons of targeted agents within a class, or studies that compare one class of agents against another,” the panel concluded. “Such trials are an important clinical priority, as are studies to mitigate side effects of these agents.”
Breast, ovarian, prostate, and pancreatic cancers are associated with pathogenic variants in BRCA1 and BRCA2 as mentioned in the presentation.
Now, it was found that more cancer types are associated with BRCA 1 and 2.
Pathogenic variants in BRCA1 were associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.
The study results suggest that the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than that determined from previous analyses, potentially indicating the broader clinical relevance of BRCA1/2 genetic testing.
jamanetwork.com/journals/jamaoncology/fullarticle/2791277
Treatment with sacituzumab tirumotecan significantly improved progression-free survival (PFS) and overall survival (OS) when compared to chemotherapy for patients with heavily pretreated, advanced triple-negative breast cancer, according to phase 3 data presented at the 2024 ASCO Annual Meeting.
The antibody-drug conjugate sacituzumab tirumotecan targets TROP2, which is overexpressed in triple-negative breast cancer and often correlates with adverse outcomes. In a phase 3 study, researchers assigned 263 patients with advanced triple-negative breast cancer to monotherapy with sacituzumab tirumotecan (n = 130) or to physician’s choice chemotherapy (n = 133).
The median age of the study cohort was 51 years, and the heavily pretreated population had received two or more previous therapies, including at least one therapy in the metastatic setting. In total, prior PD-1/PD-L1 inhibitors receipt was 26%, and 48% had received three or more lines of prior chemotherapy in the advanced setting. The rate of visceral metastases was 87%.
PFS served as the primary endpoint. Results of an interim analysis revealed that assignment to sacituzumab tirumotecan correlated with a 69% reduction in the risk of progression or death (hazard ratio [HR] = 0.31; 95% CI, 0.22-0.45; P < .00001). The median PFS for patients assigned to sacituzumab tirumotecan was 5.7 months (95% CI, 4.3-7.2), compared to 2.3 months (95% CI, 1.6-2.7) for patients assigned to chemotherapy. The 6-month PFS rates were 43.4% and 11.1%, respectively. Among patients with a TROP2 H-score above 200, the median PFS with sacituzumab tirumotecan was 5.8 months, compared to 1.9 months for chemotherapy (HR = 0.28; 95% CI, 0.17-0.48).
Median follow-up for OS was 10.4 months. The researchers observed a significant trend toward improved OS for patients assigned to sacituzumab tirumotecan (median, not reached vs 9.4 months; HR = 0.53; 95% CI, 0.36-0.78; P = .0005). The objective response rate also favored sacituzumab tirumotecan (43.8% vs 12.8%).
Treatment with sacituzumab tirumotecan was well tolerated. The most common treatment-related adverse events (grade 3 or higher) included decreased neutrophil count (sacituzumab tirumotecan vs chemotherapy, 32.3% vs 47%), anemia (27.7% vs 6.1%), and decreased white blood cell count (25.4% vs 36.4%).
I am looking forward to turning 75 in a few years because I have dense breasts, and it seems to me that when in doubt, even with no symptoms, I always get recommended for unnecessary 6 month mammograms and/or unnecessary painful biopsies. At 75, I shall tell my doctor, no thanks, I'm done with this....and celebrate!!
A recent retrospective study from Seoul National University showed adjuvant endocrine therapy for low ER expression (1-10%) may not improve survival unless patients had no adjuvant radiation therapy.
The study included both pre-and post menopausal women and both tamoxifen and AIs.
www.researchsquare.com/article/rs-2013852/v1
very busy slides
ESMO 2023 Congress Abstract by MD Anderson Cancer Center reported an interesting finding: no surgery necessary after neoadjuvant therapy including radiation therapy for patients with T-2 N0-1 triple negative or HER2+ early breast cancer:
Abstract 243MO
Background
Neoadjuvant systemic therapy (NST) for triple-negative breast cancer (TNBC) and HER2+ breast cancer (HER2+BC) yields a pathol-ogic complete response (pCR) in approximately 60% of patients. A pCR to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). Radiotherapy alone, without breast surgery after NST among patients who had a VACB-determined pCR was evaluated in the feasibility phase (Johnson et al. JACS 2023 ), 2-year pre-planned primary outcome (Kuerer et al Lancet Onc 2022 ), the 32.4 mo patient reported outcomes (Johnson et al SSO 2023 ) and now at the preplanned 3-year primary endpoint.
Methods
This multicentre phase II clinical trial enrolled women aged ≥40 years with unicentric cT1-2N0-1M0 TNBC or HER2+BC and a residual breast lesion
On March 3, 2023, the FDA approved abemaciclib with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence.
Patients defined as high risk included those having either ≥4 pALN (pathologic axillary lymph nodes) or 1-3 pALN and either tumor grade 3 or a tumor size ≥50 mm.
Abemaciclib was previously approved for the above high-risk population with the additional requirement of having a Ki-67 score ≥20%. FDA removed the Ki-67 testing requirement.
What steps would you need to take to develop an immunohistochemical method to identify breast cancer in breast tissues removed from a patient?
Monarch E trial: the latest (5-yr follow up) report:
The combination of adjuvant abemaciclib plus endocrine therapy significantly reduced the risk of long-term recurrence and improved invasive disease-free survival (DFS) for patients with HR-positive, HER2-negative, high-risk early breast cancer, according to a 5-year efficacy analysis of the monarchE study presented at ESMO Congress 2023.
The high risk factors were described in the lecture above.
The FDA approved olaparib as an adjuvant treatment in patients with deleterious or suspected deleterious germline BRCA mutated HER2-negative high-risk early breast cancer who were pretreated with neoadjuvant or adjuvant chemotherapy, according to a press release.
Olaparib is a PARP inhibitor. The recommended dose of olaparib is 300 mg orally twice daily for up to one year.
This approval was based on results from the OlympiA trial of 1,836 patients with gBRCA mutated HER2-negative high-risk early breast cancer. The primary efficacy endpoint was invasive disease-free survival.
After 3 years, invasive disease-free survival for patients receiving olaparib was 86% and just 77% for patients on placebo.
When looking at overall survival, there were 75 deaths in the olaparib arm compared to 109 deaths in the placebo arm.
October 2023:
Despite the proven benefit of adding an immune checkpoint inhibitor (ICI) to preoperative chemotherapy for patients with triple-negative breast cancer (TNBC), for example, pembrolizumab, the NeoTRIP Michelangelo trial using atezolizumab stumbled at the finish line, showing that adding atezolizumab (Tecentriq) to nab-paclitaxel and carboplatin followed by surgery and adjuvant anthracycline-based chemotherapy did not improve 5-year event-free survival (EFS), compared with the same regimen without atezolizumab.
The FDA approved olaparib for the treatment of patients with high-risk HER2- early breast cancer and germline BRCA mutations in March 2022 based on OlympiA trial. Patients had neo- or adjuvant chemotherapy followed by Olaparib for 1 year as an adjuvant therapy, which was published in NEJM.
www.nejm.org/doi/full/10.1056/NEJMoa2105215
Compared with placebo, treatment with olaparib led to a 42% reduction in the risk for invasive breast cancer recurrence, new cancer, or death (HR = 0.58; 95% CI, 0.41-0.82; P < .0001).
Now, the European Medicines Agency’s Committee for Medicinal Products in Human Use recommended the approval of olaparib as an adjuvant treatment for patients with high-risk HER2-negative early breast cancer with germline BRCA mutations in August 2022.
New Breast Cancer Screening Guideline by USPSTF
May 10,2023
USPSTF proposed reducing the recommended start age for routine screening mammograms from age 50 to age 40. The latest recommendation, which carries a B grade, also calls for screening every other year and sets a cutoff age of 74.
The task force's A and B ratings indicate strong confidence in the evidence for benefit, meaning that clinicians should encourage their patients to get these services as appropriate.
The influential federal advisory panel last updated these recommendations in 2016. At the time, USPSTF recommended routine screening mammograms starting at age 50, and gave a C grade to starting before that.
I mentioned the EMERALD trial showing improved DFS with elacestrant, a new SERD.
Now, elacestrant was approved by FDA on 1/27/2023 for post menopausal metastatic HR(+) HER2(-) and ESR1 mutation(+) breast cancer progressed over at least 1 endocrine therapy. ESR mutation can be tested by Guardant 360 CDX test.
It’s based on EMERALD trial.
ascopubs.org/doi/full/10.1200/JCO.22.00338
In June 2022 American Society of Clinical Oncology (ASCO) Annual Meeting:
PALOMA 2 trial final report:
Palbociclib (Ibrance) + lettozole was not better than letrozole alone in overall survival.
It is a surprising news as ribociclib showed survival benefit.
New approval for metastatic ER+ HER2- breast cancer in November 2023.
The US Food and Drug Administration (FDA) has approved capivasertib (Truqap, AstraZeneca Pharmaceuticals) with fulvestrant for certain previously treated adults with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative, locally advanced or metastatic breast cancer.
Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.
The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.
Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor-based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.
Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.
In the 289 patients with PIK3CA/AKT1/PTEN-altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months vs 3.1 months in the placebo group (hazard ratio [HR], 0.50).
An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN-alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% CI, 0.61-1.02), indicating that "the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN-alteration," the FDA explained.
Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.
The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.
can we get the slides please
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I would like to clarify RxPonder Trial by SWOG:
In ER+ HER2- LN1-3 + early breast cancer and Oncotype DX RE 0-25:
Post menopausal women: endocrine Tx alone (no benefit by adding chemotherapy. However, premenopausal women need endocrine and chemotherapy as the combination of endocrine and chemotherapy improved DFS.
Doc reads the slides. Saves Siri some breaths.
Dr Kim… if stage 1b TNBC / lesion 8mmx4mm found ~ in rt breast ~ on routine mammogram ~ had neoadjunctice TC CHEMO prior to double Mastectomy ( profilactic ) NEG Sentinal nodes and Lymph nodes on surgical pathology report… no suspicious nodes found prior to treatment with complete tumor response to chemo….QUESTION: Sentinal Node and Lymph node biopsy ( blue dye) was done
ONLY after neoadjunctive
chemo… could micro seedlings of cancer cells in nodes even have been determined in said nodes if they were already dead
from prior chemo therapy ⁉️⁉️
⁉️⁉️⁉️
neoadjuctive therapy; would microseedlings to
Congratulations!
No worry about Micro seeding.
For metastatic HER2 (+) breast cancer, the first line treatment is THP (Taxotere, Herceptin , Perjeta) which provides objective response rate of 80% and overall survival almost 5 years.
Now, Destiny-Breast 03 trial report shows Enhertu (trastuzumab emtansine) was superior to Kadcyla (trastuzumab deruxtecan).
But there is no randomized study directly comparing THP with Enhertu (trastuzumab emtansine).
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended trastuzumab deruxtecan for approval in the treatment of adults who have unresectable or metastatic HER-2 positive breast cancer in the European Union.
“This recommendation reflects the transformative progression-free survival benefit seen in the DESTINY-Breast03 trial compared to Enhertu (trastuzumab emtansine) supporting Kadcyla (trastuzumab deruxtecan) as a potential new standard of care and setting a new benchmark in the treatment of HER2-positive metastatic breast cancer.
In the phase 3, randomized DESTINY-Breast03 trial, researchers reported that 75.8% (95% CI, 69.8-80.7) of patients assigned to trastuzumab deruxtecan were alive without disease progression at 1 year, compared with just 34.1% (95% CI, 27.7 to 40.5) of those assigned to trastuzumab emtansine, meaning those assigned to the former were at a 72% reduced risk for death (HR = 0.28; 95% CI, 0.22-0.37; P < .0001).
Furthermore, the researchers continued, 94.1% (95% CI, 90.3 to 96.4) of patients assigned to trastuzumab deruxtecan were alive at 1 year, compared with 85.9% (95% CI, 80.9 to 89.7) among those assigned to trastuzumab emtansine.
Stereotactic ablative body radiotherapy (SABR) for Oligometastasis
Stereotactic ablative body radiotherapy (SABR) appeared to delay the need for changes in systemic therapy in postmenopausal patients with oligoprogressive luminal ER-positive, HER2-negative breast cancer, according to a new phase 2 study.
In the AVATAR trial, patients with one to five metastatic lesions who’d been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and aromatase inhibitors for at least 6 months underwent SABR. Of those, 47% had event-free survival of more than 6 months.
Participants could not have had leptomeningeal disease, previous chemotherapy for metastatic disease, or prior radiotherapy to an oligoprogressing lesion. Most metastases were to bone (n = 44, 71%), node (systemic, n = 8; 13%) and lung (n = 4; 6%).
The patients were treated with SABR, most commonly 24 Gy (n = 25; 43%) and 20 Gy (n = 10; 17%); half had one lesion treated (50%), and 25% had two lesions treated.
The median follow-up was 15.8 months. The median event-free survival was 5.2 months (95% confidence interval, 3.1-9.4 months), with events defined as progression within 6 months or in at least three lesions. Fifteen patients (47%) reached event-free survival of 6 or more months.
Median modified progression-free survival was 10.4 months, and median progression-free survival was 5.2 months; 31% of patients received SABR for further oligoprogression, and 46% patients remained on CDK4/6 inhibitors and aromatase inhibitors for 12 months. Overall survival was 100%.
A total of 14 patients had grade 1 adverse events, 2 had grade 2 events, and none had grade 3 or higher events; 47% had no treatment-related toxicity.
However, further randomized trials are required before routine implementation in clinical practice. For now, patients should be considered in a case by case basis with multidisciplinary discussion to determine the optimal systemic therapy regimen at oligoprogression and whether SABR may provide benefit.
Sacituzumab govitecan is approved by FDA for metastatic triple negative breast cancer.
A recent study (TROPiCS-02) showed it may be effective for ER + metastatic breast cancer.
The first analysis of the phase 3 TROPiCS-02 study, showed that patients on sacituzumab govitecan had a median progression-free survival of 5.5 months compared to 4 months for patients on physician choice chemotherapy. At 12 months, 21% of patients were free of disease progression and alive in the sacituzumab arm compared to 7% of patients in the chemotherapy arm.
meetings.asco.org/abstracts-presentations/206927
SG (vs TPC) improved median PFS (5.5 vs 4.0 mo; HR, 0.66; 95% CI, 0.53-0.83; P= 0.0003); PFS rates at 6 and 12 mo were 46% vs 30% and 21% vs 7%, respectively. SG vs TPC showed a numeric but nonsignificant difference in OS (13.9 vs 12.3 mo; HR, 0.84; P= 0.143); ORR (21% vs 14%) and clinical benefit rate (34% vs 22%) were higher with SG vs TPC and median duration of response was 7.4 vs 5.6 mo, respectively. Overall, 74% vs 60% of patients (SG vs TPC) had grade ≥3 treatment-emergent adverse events (AEs); neutropenia (51% vs 39%) and diarrhea (10% vs 1%) were most common. AEs leading to discontinuation of SG vs TPC were low (6% vs 4%).
The choice of fulvestrant as endocrine therapy did not significantly improve overall survival (OS) compared to anastrozole among postmenopausal patients with HR-positive advanced breast cancer who were naive to endocrine therapy.
According to the final analysis of the FALCON study presented at ESMO Congress 2023.
However, for non-visceral metastatic disease, fulvestrant showed better overall survival than anastrazole which was not statistically significant.
www.annalsofoncology.org/article/S0923-7534(23)01397-2/fulltext
Please HELP!!! I'm 72 years old with neuroendoccrine breast carcinoma 3.1cm stage 2 poorly differentiated. I'm aware its a very agressive cancer. I had lumpectomy and my surgeon confirms that lymphs nodes were negative er+ pr+ her2- . All tissue around cancer margins very good. I saw two oncologists, one for radiation and the other for chemo. They don't know if I will benefit from chemo but I will have radiaton and hormones therapy. What kind of treatment do you think I should have and what are prognostic for this kind of cancer if I take chemo??? I'm in a good health but I want to have quality of life too and if treatment won't help to live longer then I would refuse chemo treatment. COULD IT BE A PRIMARY CANCER IF THEY DON'T SEE ANYTHING ON SCANS like nuclear bone, ct scan for abdo chest and brain???
It’s a very rare cancer that no oncologist can say confidently about how to treat. So we follow the general rule of common breast cancer therapy.
With no lymph node metastasis and relatively small size tumor which was resected completely, I would say it is fortunate. Please have your oncologist check for the ki-67 index of the cancer. If is over 10%, chemotherapy may help. The high ki-67 index means more aggressive cancer which responds to chemotherapy. Age didn’t matter, many elderly patients tolerate it well especially otherwise healthy people like you.
Because of + ER, endocrine therapy is important.
God luck and God bless you!
Thank you for your response. At the beginning my oncologist admitted he didn't know how to treat me. He phone me and says he wants me to do 4 rounds of strong chemo and then 12 less strong treatment. Then its 3 weeks radiation and 1 week booster. He told me that if i don't take treatments I have 80% chance of reccurence. When i do research the rate for survival between chemo and no treatments is not much. I don't know what to do. Is it worth it having to deal with all the side effects!!!
An interesting article was just published in the American Cancer Society journal regarding higher stages of ER+ HER2- Invasive lobular carcinoma (ILC) requiring chemotherapy:
Neoadjuvant or adjuvant chemotherapy did not improve cancer specific and overall survival (as long as they have endocrine therapy).
In other words, patients with ER+, HER2-, ILC who will have endocrine therapy may not need neo- adjuvant chemotherapy.
However, this result has to be confirmed before considering the standard of care.
acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35125
KEYNOTE-355 Update Report:
In November 2020 FDA approved pembrolizumab in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥10). It was based on improved progression free survival not based on the overall survival data.
Now the updated report was published confirming the benefit of pembrolizumab+chemotherapy in improving overall survival.
www.nejm.org/doi/full/10.1056/NEJMoa2202809
How can I get the ppt presentation
How can I get the ppt presentation ?
Adjuvant radiation therapy (ART) in breast cancer conservation therapy for stage 1-2 patients (
The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD).
Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren't effective or can't be tolerated. It's also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.
This new warning updates a November 2022 alert based on preliminary evidence for a "substantial risk" for hypocalcemia in patients with CKD on dialysis.
Finally the result of MonarchE trial with the 5 year follow up was presented in 2023 ESMO.
Results of a planned 5-year efficacy analysis of the monarchE trial showed that at a median follow-up of 4.5 years, the abemaciclib/endocrine therapy combination was associated with a 7.6% absolute improvement in invasive disease-free survival (IDFS) and 6.7% edge in distant relapse-free survival (DRFS), compared with endocrine therapy alone
The monarchE trial included two cohorts: a primary cohort consisting of patients deemed at high risk based on clinical pathological features such as the number of involved axillary nodes, grade 3 disease, and tumors 5 cm or larger, and a second cohort of patients with lower disease grade and smaller tumors but with high levels of the proliferation marker Ki-67.
A total of 5,637 patients were randomized to receive either 2 years of abemaciclib 150 mg twice daily plus endocrine therapy, or endocrine therapy alone, followed by 3-8 years of additional endocrine as clinically indicated in each study arm.
An earlier preplanned interim analysis of the phase 3 trial of more than 5,600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.
As that analysis showed, at a median follow-up of 15.5 months abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of IDFS vs. endocrine therapy alone.
The IDFS benefit with the combination was consistent across most subgroups, including older patients, perimenopausal and postmenopausal patients, those who had received prior neoadjuvant or adjuvant chemotherapy, all tumor sizes, number of positive lymph nodes, less favorable tumor stage or grade, and order of endocrine therapy (tamoxifen or aromatase inhibitor as first drug).
As noted before, DRFS, a secondary endpoint, also favored abemaciclib, with 345 events occurring over 5 years in the combination arm, compared with 501 in the endocrine therapy arm alone. This translated into a HR with the combination of 0.68 (P < .001).
The proportions of patients with treatment-emergent adverse events and serious adverse events (SAEs) were higher in the combination arm than in the endocrine therapy alone arm in all previous analyses of the trial data.
The NATALEE trial, in which patients were randomized to endocrine therapy with or without the CDK4/6 inhibitor ribociclib (Kisqali) was previously shown to provide a significant survival advantage for women with both high-risk and intermediate-risk patients with early breast cancer: the absolute difference in 3-year IDFS rates between the combination group and endocrine monotherapy groups was 3.3%.
To determine the ultimate value of combining a CDK4/6 inhibitor with endocrine therapy in early breast cancer, longer follow-up of both trials will be necessary.
Questions that still need to be answered include the optimal duration of CDK4/6 inhibitor therapy, whether adjuvant therapy should be resumed when there are signs of renewed proliferation, and whether there would be a benefit to restarting CDK4/6 inhibitors when metastasis occurs.
Triple negative breast cancer stage 1 may not need neoadjuvant or adjuvant chemotherapy if stromal tumor infiltrating lymphocytes (TIL) are over 50%.
jamanetwork.com/journals/jamaoncology/article-abstract/2820527
After neoadjuvant therapy for early HER2 (+) breast cancer, breast conservation therapy provides better overall survival than mastectomy among patients who achieved pathological complete response (pCR) in the axillary lymph nodes. But among patients with pCR in the breast, the survival did not differ.
www.thelancet.com/journals/lanam/article/PIIS2667-193X(24)00039-5/fulltext#%20
In postmenopausal women treated for early-stage estrogen receptor-positive breast cancer, neither Vaginal estrogen therapy (VET) nor MHT (menopausal hormone therapy) was associated with increased risk of recurrence or mortality. A subgroup analysis revealed an increased risk of recurrence, but not mortality, in patients receiving VET with adjuvant aromatase inhibitors.
academic.oup.com/jnci/article/114/10/1347/6645744?login=false
However, a subgroup analysis revealed an increased risk of recurrence, but not mortality, in patients receiving VET with adjuvant aromatase inhibitors (but not with tamoxifen).
Partial breast irradiation is recommended over whole breast irradiation for ‘’node negative ER + early breast cancer.
The American Society for Radiation Oncology (ASTRO) has issued an updated clinical practice guideline on partial breast irradiation for women with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS).
The 2023 guideline, which replaces the 2017 recommendations, factors in new clinical trial data that consistently show no significant differences in overall survival, cancer-free survival, and recurrence in the same breast among patients who receive partial breast irradiation compared with whole breast irradiation. The data also indicate similar or improved side effects with partial vs whole breast irradiation.
For patients with early-stage, node-negative invasive breast cancer, the updated guideline strongly recommends partial breast irradiation instead of whole breast irradiation if the patient has favorable clinical features and tumor characteristics, including grade 1 or 2 disease, estrogen receptor (ER)-positive status, small tumor size, and age 40 or older.
The updated guideline also conditionally recommends partial over whole breast irradiation if the patient has risk factors that indicate a higher likelihood of recurrence, such as grade 3 disease, ER-negative histology, or larger tumor size.
The task force does not recommend partial breast irradiation for patients with positive lymph nodes, positive surgical margins, or germline BRCA1/2 mutations or patients under 40.
Given the lack of robust data in patients with less favorable risk features, such as lymphovascular invasion or lobular histology, partial breast irradiation is conditionally not recommended for these patients.
For DCIS, the updated recommendations mirror those for early-stage breast cancer, with partial breast irradiation strongly recommended as an alternative to whole breast irradiation among patients with favorable clinical and tumor features, such as grade 1 or 2 disease and ER-positive status. Partial breast irradiation is conditionally recommended for higher grade disease or larger tumors, and not recommended for patients with positive surgical margins, BRCA mutations or those younger than 40.
Recommended partial breast irradiation techniques include 3-D conformal radiation therapy, intensity modulated radiation therapy, and multicatheter interstitial brachytherapy, given the evidence showing similar long-term rates of ipsilateral breast recurrence compared with whole breast irradiation.
Single-entry catheter brachytherapy is conditionally recommended, and intraoperative radiation therapy techniques are not recommended unless integrated into a prospective clinical trial or multi-institutional registry.
The guideline also outlines optimal dose, fractionation, target volume, and treatment modality with different partial breast irradiation techniques, taking toxicities and cosmesis into consideration.
Atezolizumab didn’t help to improve pathological complete response rate for HER (+) high risk breast cancer when added to classical dose dense AC-T in a neoadjuvant setting.
ascopubs.org/doi/full/10.1200/JCO.21.02772?bid=183384593&cid=DM10951
So far,
Breast conservation therapy is feasible for ipsilateral multiple breast cancer: local recurrence about 3% in 5 years, not different from single tumor.
ascopubs.org/doi/abs/10.1200/JCO.22.02553?journalCode=jco
Exemestane + ovarian suppression is better than tamoxifen + ovarian suppression or tamoxifen alone in premenopausal ER+ HER2- early invasive lobular breast cancer
www.medscape.com/viewarticle/exemestane-plus-ovarian-suppression-best-early-invasive-2024a10009tv
However, it is not clear if patients with invasive ductal breast cancer can have de-escalated therapy such as tamoxifen alone.
Neoadjuvant therapy for TNBC with carboplatin, Docetaxel and pembrolizumab
jamanetwork.com/journals/jamaoncology/article-abstract/2812294
The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.5 This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m2), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC. The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%).
An interesting study of adjuvant endocrine therapy for hormone receptor (+) premenopausal patients: 2 years of goserelin (Zoladex: GnRH agonist) alone is good enough for genomic high risk group over combination of goserelin + tamoxifen. The combination caused more side effects and intersection without benefit.
Tamoxifen alone benefits genomically low risk group.
ascopubs.org/doi/full/10.1200/JCO.21.02844?bid=188486727&cid=DM11130
8 years of follow up after neratinib (HER2 TK inhibitor) adjuvant therapy, overall survival was not different from placebo group.
Although neratinib improved invasive disease free survival, it did not improve overall survival.
www.ejcancer.com/article/S0959-8049(23)00063-1/fulltext#:~:text=Eight%2Dyear%20overall%20survival%20rates,1.21%3B%20p%20%3D%200.6914).
PET-CT Scanning Improves Detection of Metastases in Patients With Locally Advanced Breast Cancer (Stage llB; T3N0 - Stage lll)
ascopubs.org/doi/full/10.1200/JCO.23.00249?journalCode=jco
Data suggest that whole-body PET-CT scanning may act as a superior method for detecting distant metastases and identifying patients who would benefit from less aggressive therapy.
The researchers randomly assigned patients to whole-body 18F-labeled fluorodeoxyglucose PET-CT scanning or conventional staging methods. Upstaging to stage IV metastatic disease served as the study’s primary endpoint. Receipt of multimodal therapy served as a key secondary endpoint.
The study included data from 369 patients (PET-CT, n = 184; conventional staging, n = 185). A significantly higher percentage of patients assigned to PET-CT scanning were upstaged to stage IV than patients assigned to conventional staging (23% vs. 11%; relative risk, 2.4; 95% CI, 1.4-4.2; P = .002).
In the PET-CT arm, the most common sites for distant metastases among upstaged patients included bone (alone, = 14; plus another site, n = 15), mediastinal nodes (alone, n = 3; plus other site, n = 11), liver (alone, n = 2; plus another site, n = 4), and lung (alone, n = 3; plus another site, n = 7). Bone was the most common site of metastases in the conventional staging arm (alone, n = 6; plus another site, n = 8).
Although the researchers did not consider cancer detection in regional nodes a basis for upstaging, they noted that a significantly higher percentage of upstaged patients in the PET-CT arm had positive regional nodes compared to upstaged patients in the conventional staging arm (97.7% vs. 61.9%; P = .03).
In total, 81.3% of upstaged PET-CT patients (n = 35 of 43) and 95.2% of upstaged conventional staging patients (n = 20 of 21) had their intended treatment platform changed. Nineteen percent of patients assigned to PET-CT scanning did not receive combined modality treatment, compared to 11% of patients assigned to conventional staging (absolute difference, 8.2%; 95% CI, 0.1-15.4; P = .03).
PostMONARCH trial: abemaciclib + fulvestrant is better than placebo + fulvestrant for ER + HER2- metastatic breast cancer progressed over previous CDK4/6 inhibitor plus endocrine therapy.
ORR16%, PFS at 6 Mon. 50%.
www.medscape.com/s/viewarticle/abemaciclib-combo-improves-survival-advanced-breast-cancer-2024a1000anu?ecd=WNL_clinicdgst_240731_MSCPPERSO_6712876_pos1&uac=289993FT&impID=6712876&form=fpf
No OS Benefit with Margetuximab Over Trastuzumab in Previously Treated HER2+ Breast Cancer
Final overall survival results from the phase 3 SOPHIA trial revealed that the progression-free survival advantage seen with margetuximab over trastuzumab in an earlier analysis did not translate into a significant OS benefit in patients with previously treated HER2-positive metastatic breast cancer.
The earlier PFS analysis of the study led to FDA approval of margetuximab with chemotherapy in patients with HER2-positive metastatic breast cancer who have received at least 2 prior anti-HER2 regimens-at least one of which was for metastatic disease.
A total of 536 patients in the intention-to-treat population were randomly assigned to treatment with either IV margetuximab (15 mg/kg once every 3 weeks; n = 266) plus chemotherapy or IV trastuzumab (6 mg/kg once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy.
The final OS analysis was triggered by a total of 385 deaths, which had occurred at a median follow-up of 20.2 months. At that point, it was found that median OS was 21.6 months among patients treated with margetuximab, compared with 21.9 months among their counterparts treated with trastuzumab.
The researchers also performed a pre-planned subgroup analyses of OS by type of chemotherapy and HER2 status, which showed no difference in survival between margetuximab and trastuzumab.
On the other hand, an exploratory analysis of CD16A genotyping suggested a possible OS improvement among CD16A-158FF patients treated with margetuximab (median 23.6 months) relative to trastuzumab (median 19.2 months; HR = 0.72; 95% CI, 0.5-1).
Similar analyses revealed a possible OS benefit for trastuzumab in CD16A-158VV patients relative to margetuximab (median OS 31.1 vs 22 months; HR = 1.77; 95% CI, 1-3.1).
Safety analyses found that margetuximab was comparable with trastuzumab. Treatment discontinuation due to adverse events were observed in 4% of patients in each treatment group.
In light of these findings, the investigators wrote that the PFS advantage previously observed with margetuximab-chemotherapy did not translate into a significant difference in OS in the intention-to-treat population of the SOPHIA trial.
They added that further studies of margetuximab in patients with HER2+ breast cancer with different CD16A allelic variants are warranted.