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SABCS 2022 | The molecular differences between younger versus older ER-positive and HER2-negative breast cancers

Lajos Pusztai, MD, Yale School of Medicine, New Haven, CT, discusses the molecular differences between younger versus older ER-positive, HER2-negative breast cancers and how this relates to response to chemotherapy. The Phase III RxPONDER (NCT01272037) and the Phase III TAILORx (NCT00310180) trial previously demonstrated benefit from adjuvant chemotherapy but no benefit in older women with the same clinical features. In the current analysis, the findings suggest that HR-positive, HER2-negative breast cancer in younger patients may have higher chemotherapy sensitivity due to greater immune infiltration in the tumor microenvironment compared to cancers in older women. Additionally, younger woman have lower endocrine sensitivity based on an observed ER signature. Chemotherapy sensitivity and endocrine sensitivity were observed to be mutually exclusive in this patient population. It was concluded that younger woman with a high immune presence in the TME benefit directly from the cytotoxic effect of chemotherapy, whereas younger woman with a low immune presence and endocrine sensitivity benefit from the ovarian suppressive function of chemotherapy. This interview took place at the San Antonio Breast Cancer Symposium (SABCS) 2022 in San Antonio, TX.

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