Cynthia Ma, MD, PhD, Washington University, St. Louis, MO, discusses the neoadjuvant options available for patients with HR-positive, breast cancer, a topic she presented at the 2022 San Antonio Breast Cancer Symposium.

Dr Ma reviewed data from multiple studies investigating various subgroups of this patient population that may help clinicians to select the optimal neoadjuvant therapy.

Transcript

My name is Dr Cynthia Ma, I'm a professor of medicine from Washington University in St Louis.  At the 2022 San Antonio Breast Cancer Symposium at the education session, I presented on neoadjuvant therapy for ER-positive breast cancer and potential implications on outcomes and prognosis.

I went over data that breast cancer for the ER-positive, HER2-negative breast disease is a heterogeneous group of diseases. In the adjuvant setting we have chemotherapy, CDK4/6 inhibitors, and endocrine therapy. In the neoadjuvant setting, how to choose these agents, there's no strict guidelines. We discussed that chemotherapy tends to be less sensitive in this patient population. We know that many patients probably do not need chemotherapy, based on the TAILORx, RxPONDER and MINDACT trials in the adjuvant setting. It does not make sense that we give the majority of patients chemotherapy in the neoadjuvant setting.

In addition, we talked about pathologic complete response rate in the neoadjuvant setting for postmenopausal women with ER-positive breast cancer being low and not prognostic for long term outcomes. We focused a lot of the discussion on neoadjuvant endocrine therapy since it has shown to effectively downstage the tumor, especially in postmenopausal women, and to a rate that improves the breast conservation surgery similar to that for chemotherapy. Aromatase inhibitors are better than tamoxifen in downstaging the tumor for that purpose.

We also discussed that in addition to facilitating the breast cancer surgery, potentially on-treatment biomarker analysis such as Ki-67 could serve as a prognostic marker, and this has been studied retrospectively as well as most recently prospectively by the POETIC trial. Two-week Ki-67 assessment on tumor biopsy during neoadjuvant endocrine therapy serves as a prognostic marker. Patients with Ki-67 over 10% – indicating persistent cell proliferation resistant to endocrine therapy –tend to do worse, with the worst 5-year recurrence-free survival. However, those with decreased Ki-67 at week 2 have a better prognosis than those who have consistent, persistently elevated Ki-67.

We also talked about preoperative endocrine prognostic index (PEPI). This includes Ki-67 as well as surgical pathologic factors. And a PEPI score of 0 is prognostic for excellent prognosis. We went over data reported from the ALTERNATE trial that enrolled patients – post-menopausal women with ERH, HER2-negative breast cancer — to either an anastrozole, or fulvestrant, or the combination. We demonstrated that the combination therapy is more effective in the luminal B population. In the luminal A population, an aromatase inhibitor by itself is effective, so the combination perhaps is not needed.

We also showed that non-luminal breast cancer patients do not respond to endocrine therapy. The rate of very high Ki-67 at 2 weeks is much higher than other subtypes. We also went over CDK4/6 inhibitor trials. These remain investigational, and there are prospective studies looking at whether response to neoadjuvant CDK4/6 inhibitor could tailor the use of chemotherapy. The optimal end point is still unknown, so these are investigational.

We concluded that neoadjuvant endocrine therapy is potentially appropriate for patients who have low grade, or low genomic risk, post-menopausal, with the ER-positive breast cancer, and chemotherapy potentially could benefit from those with non-luminal breast cancers. We still need prospective trials to specifically address whether the genomic signature would be beneficial in the purpose of downstaging the tumor.

Source:

Ma C. “Predictive value of treatment response and residual disease after neoadjuvant therapy – hormone receptor positive breast cancer.” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas.