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Traditionally, neoadjuvant chemotherapy has been used to downstage locally advanced and unresectable primary breast tumors to make them operable.1,2 Endocrine therapy has emerged as an attractive alternative in the neoadjuvant setting for postmenopausal women with estrogen receptor–positive (ER+) breast cancer, with comparatively less toxicity. Direct comparison between neoadjuvant chemotherapy and endocrine therapy has not been addressed in large randomized studies as the selection of patients for either treatment has to date been based upon menopausal status and ER status of the tumor. One Russian study randomized 121 postmenopausal women with T2-4 ER+ and/or progesterone–receptor-positive (PR+) breast cancer to receive either neoadjuvant doxorubicin and paclitaxel chemotherapy (n = 62) or neoadjuvant endocrine treatment with anastrozole (n = 30) or exemestane (n = 29) for 3 months prior to surgery.3 Clinical and mammographic objective response rates (ORR) were similar for endocrine therapy and chemotherapy, and there was a trend for greater rates of breast-conserving surgery with endocrine therapy with no significant differences in local recurrence rates at 34 months. Grade 3/4 alopecia, neutropenia, cardiotoxicity, and neuropathy were experienced by significant numbers of women in the chemotherapy group. Neoadjuvant endocrine therapy was better tolerated, the most common adverse events being hot flushes, fatigue, vaginal bleeding, and arthralgia. These data support the view that endocrine therapy is a safe alternative to chemotherapy, with similar response rates but less toxicity. In ER+ breast cancer there is also some evidence to suggest that neoadjuvant chemotherapy is less effective than in ER– breast cancer. A recent retrospective study of 1731 patients who had primary chemotherapy showed a significantly lower rate of pathologic complete response to chemotherapy in patients with hormone receptor–positive tumors compared with those with hormone receptor–negative tumors (8% vs 24%; p < .0001).4 These data are consistent with the observation that patients with hormone receptor–positive disease are less chemosensitive and respond better to endocrine therapy. There is also evidence to suggest that the histological response to chemotherapy and endocrine therapy differ, with higher rates of central scarring in tumors treated with neoadjuvant letrozole (58.5% vs 2%, p = .035).5 Central scarring correlates with clinical response and explains why, following endocrine therapy, excising the residual mass results in complete excision more often than after neoadjuvant chemotherapy where scattered widespread foci of disease are significantly more common.5 In this study, complete pathological response rate, as expected, was seen significantly more frequently after neoadjuvant chemotherapy, although this was not seen in the randomized study by Semiglazov.3

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With careful selection there are benefits of neoadjuvant therapy compared with primary surgery. The most significant benefits are in postmenopausal patients with large operable or locally advanced inoperable ER+ tumors, which can be downstaged to become operable or to be suitable for less extensive surgery, such as breast conservation in those originally thought to require mastectomy. It is widely accepted that breast conservation followed by radiotherapy provides improved quality of life, better cosmetic outcomes, and comparable disease control compared with ...

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