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What are your top takeaways from SABCS 2023?

4 Answers
Mednet MemberInvited Expert
Radiation Oncology · University of Texas MD Anderson Cancer Center
Answered on
  1. The B51 trial surprised the radiation oncology community, showing that in patients with an exceptional response to systemic therapy, radiation to the regional nodes did not result in a significant improvement in the invasive breast cancer recurrence free interval nor the isolated loco-regional recurrence free interval. Perhaps the most interesting finding was that on subset analysis, the ER+ and Her-2 positive patients appeared to have a greater benefit from RNI than triple negative patients, which is contrary to prior findings from MA.20 and Alliance 1071 trials, which both showed a benefit of RNI in patients with triple negative breast cancer in subset analyses. On B51, there was a trend for a higher benefit of RT in patients with mastectomy and there was no subset analysis of patients with ITCs present, thus review of the full manuscript is recommended before making a blanket change in radiation recommendations for this group of patients.

  2. The IDEA trial showed that in biologically favorable hormone positive breast cancer patients as young as 50, the risk of recurrence with lumpectomy alone was very low, less than 5%. This study has a short follow-up and patients were relatively young, thus the results are not necessarily practice-changing, however, it does provide support for the ongoing DEBRA trial, which is a large randomized trial looking at omission of radiotherapy in a similar biologically favorable post-menopausal population. This randomized study will look not only at oncologic endpoints, but also at quality-of-life issues, such as anxiety about recurrence in patients who omit radiation. Also of note, while most patients during the accrual of IDEA were likely given the option of 4 weeks whole breast radiation versus trial participation, a five fraction partial breast radiation regimen is now a standard treatment option for these low risk patients.  This shorter course of radiotherapy to a more limited field provides minimal toxicity, as well as lower financial and social stress than historic whole breast regimens. Therefore, the perceived benefits of omission of radiotherapy may not be as high in the current era.

  3. The Z11 and AMAROS trials markedly changed surgical practice for many breast cancer patients, showing a lack of benefit for ALND in patients who were receiving radiation as a component of their care. However, there were few patients in these trials with mastectomy and a large portion of patients had minimal nodal disease burden, with only 41% of Z11 patients and 60% of AMAROS patients having macrometastses. The SENOMAC trial randomized 2,450 patients with cT1-T3N0 tumors with 1-2 positive macrometastases on SLNBx to no further surgery vs ALND. An impressive 20% of patients had lobular carcinoma and 34% had ENE, making this population a much higher risk group than the aforementioned trials. Additionally, 36% of patients underwent mastectomy, as compared to 0% on Z11 and 18% on AMAROS. Similar rates of radiotherapy were used in both arms of the SENOMAC trial, approximately 88%. There was no difference in recurrence free survival between the two arms. Subset analysis looking at age, T stage, number of macrometastases, presence of ECE, surgical approach, tumor subtype, and lobular histology showed no group that benefited from ALND. With these results, it is expected that patients with cT1-3N0 disease who are found to have 1-2 macrometastases on SLNBx can be spared ALND, though it remains to be determined whether ALND will be recommended to guide systemic therapy options in this population of patients and potentially de-escalate systemic therapy.
Mednet MemberInvited Expert
Medical Oncology · H Lee Moffitt Cancer Center, University of South Florida
Answered on
  1. INAVO120 study: The study looked at triplet therapy using inavolisib (PIK3CA inhibitor) plus palbociclib and fulvestrant vs. palbociclib and fulvestrant in women with metastatic ER+HER2- breast cancer that has recurred while on or within 12 months of adjuvant endocrine therapy. The progression free survival and overall survival both significantly favored the triplet combination over the doublet therapy. Toxicity as expected was greater in the triplet with more hyperglycemia, rash, and GI side effects but this did not seem to cause treatment discontinuations frequently. This data may drive new combinations of targeted agents for endocrine resistant metastatic ER+ breast cancer to improve outcomes. However, there are concerns about both medical and financial toxicity with using the INAVO120 regimen for these patients.
  2. NATALEE: This phase 3 trial studied the use of adjuvant endocrine therapy +/- ribociclib 400mg daily given 3 weeks on 1 week off for 3 years for women with stage II-III ER+HER2- breast cancer. At a median follow up of 33 months, the updated 3-year invasive disease free survival was improved in the ribociclib group vs. control (90.7% vs. 87.6%). Benefit was seen across subgroups including stage II node negative disease although the absolute benefit was less than stage III. Adjuvant ribociclib may be another treatment option for stage II-III higher risk ER+HER2- breast cancer. However, some concerns around the NNT and costs of a 3-year regimen of ribociclib will require additional predictive biomarker work to establish who truly needs this treatment.
  3. HER2 CLIMB 02: This second trial comparing TDM1 +/- tucatinib in HER2+ metastatic breast cancer demonstrated that the combination of ADC plus TKI provides superior efficacy compared to ADC alone. Furthermore, this is the second trial showing superior outcomes in patients with CNS disease when tucatinib is added to systemic therapy. This data may allow us to use this combination if patients are not suitable candidates for capecitabine.
Mednet MemberInvited Expert
Medical Oncology · Washington University School of Medicine
Answered on
  1. GS03-13: Phase III study of inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: INAVO120 primary analysis. The progression free survival improvement from adding inavolisib to the standard of care palbociclib and fulvestrant is impressive and will likely change our clinical practice in the front line therapy for this poor prognostic patient population.

  2. GS02-07: Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304. The study suggests that axillary nodes downstaging to ypN0 with neoadjuvant chemotherapy may obviate the need for reginal nodal radiation, which is the current standard.

  3. GS03-03: Ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) as adjuvant treatment in patients with HR+/HER2− early breast cancer: final invasive disease–free survival (iDFS) analysis from the NATALEE trial. With longer follow up, adjuvant ribociclib continues to demonstrate significant iDFS improvement when added to NSAI, including the stage II disease. The data is promising and hope to provide another CDK4/6 inhibitor option for patients with ER positive breast cancer, with a wider eligibility criteria than abemaciclib.
Mednet MemberInvited Expert
Medical Oncology · Ohio State University
Answered on
  1. Updated analysis of the KATHERINE trial at a median follow up of 8.4 years that continues to show clinically and statistically significant benefits of adjuvant TDM1 as compared to trastuzumab in women with HER2-positive breast cancer who have residual disease after neo-adjuvant chemotherapy. The updated analysis now showed invasive disease free as well as overall survival benefit.
  2. Final IDFS analysis of NATALEE trial that showed benefit from adding adjuvant ribociclib for 3 years to adjuvant endocrine therapy, even in women with stage IIA node negative breast cancer that has other high-risk features such as high tumor grade, Ki67 of >20%, Oncotype Dx recurrence score of >25.
  3. INAVO 120 trial that showed doubling of progression free survival and a trend towards longer overall survival (although data is still immature) in women with high-risk, hormone receptor positive metastatic breast cancer and somatic PIK3CA mutation who received inavolisib with fulvestrant compared to fulvestrant alone.