Is complete response the answer?

Overall, breast cancer mortality rates decreased by 36% from 1989 to 2012 in the United States, and similar trends have been observed in Europe [1, 2]. The improved survival is attributed to more effective systemic adjuvant therapies and, to a lesser extent, to earlier detection through mammographic screening. Yet, close to 40 000 patients experience metastatic recurrence after an initial diagnosis of stage I–III breast cancer in the United States each year, and therefore the question remains how to further improve the efficacy of adjuvant treatment. Administration of chemotherapy before surgery provides an opportunity to directly assess the cytotoxic activity of a new regimen on the primary tumor and compare it with a standard of care treatment. Not surprisingly, complete eradication of all invasive cancer from the breast and lymph nodes [i.e. pathologic complete response (pCR), ypT0/Tis, ypN0] is associated with an excellent survival at the patient level. Patients with pCR have around a 5% risk of distant metastatic recurrence in 5 years [3]. More extensive residual cancer (RD) is associated with increasingly worse survival in all breast cancer subtypes, but the strongest association is seen in triple negative cancers [3]. This is consistent with the hypothesis that the chemotherapy sensitivity of the distant micrometastases is broadly similar to that of the primary tumor. Indeed, generations of adjuvant chemotherapy regimens that were shown to improve survival also demonstrated increased pCR rates when administered as neoadjuvant therapy compared with earlier regimens (pCR_ACx4 < pCR_AC+taxane < pCR_{AC+taxane+trastuzumab} < pCR_{AC+taxane+trastuzumab+pertuzumab}).

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