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PURPOSE OF REVIEW In this article, recent developments with molecular profiling in breast cancer and future directions will be highlighted. RECENT FINDINGS Gene-expression profiling revealed four major biologic subtypes that reflect intertumoral heterogeneity of breast cancer and have led to the development of prognostic tools to facilitate adequate treatment in early breast cancer. A number of commercially available prognostic tests have been introduced for implementation in clinical routine. Also, predictive tools and approaches to characterize molecular portraits of metastatic breast cancer in order to overcome treatment resistance have been investigated. Efforts to identify the quantity and quality of clonal selection and genomic variability through modern genomic profiling led successfully to new insights into targeted treatment with more effective drugs and the promise to overcome resistance. SUMMARY Multigene approaches and novel microarray platforms such as the next-generation sequencing technology are feasible in clinical practice in order to assess the prognosis more precisely and to identify new molecular targets for developing more effective drugs in the near future.

The use of preoperative chemotherapy for breast cancer is becoming a widely accepted treatment option. Survival of breast cancer patients treated with preoperative chemotherapy has been shown to be equivalent to that of breast cancer patients treated with postoperative chemotherapy.1,2 However, preoperative therapy has advantages: it permits in vivo assessment of tumor response to chemotherapy and increases rates of breast-conserving therapy (BCT) without significantly increasing the risk of local recurrence.2 Although preoperative chemotherapy has been shown to increase the proportion of patients who are able to undergo BCT,1,3–5 several critical questions regarding this approach have not been resolved. First, it is not known whether preoperative chemotherapy versus the more common approach of postoperative chemotherapy has an effect on the volume of breast tissue resected. Until now, it has been assumed that if preoperative chemotherapy increases the proportion of patients able to undergo segmental resection rather than mastectomy, patients who receive preoperative chemotherapy will have less breast tissue excised compared with patients with the same tumor size at presentation who receive postoperative chemotherapy. However, in theory, the actual volume of tissue resected could be no different or even larger because surgeons remove a large amount of tissue in an attempt to obtain clear margins. To our knowledge, how preoperative versus postoperative chemotherapy affects the volume of tissue excised has not been formally studied. The volume of breast tissue resected in patients undergoing BCT is known to have a direct impact on cosmesis.6 Second, it has not been determined whether preoperative chemotherapy increases the number of operative procedures required to achieve negative margins. Since chemotherapy shrinks tumors in different ways and rarely concentrically, does the use of preoperative chemotherapy make obtaining clear margins more difficult and therefore result in more surgical procedures required for margin control? We performed this study to determine the effect of preoperative versus postoperative chemotherapy on the volume of tissue excised and the number of breast operations in patients undergoing surgery for breast cancer. This type of information is critically important to patients when they are considering their surgical options and the risks and potential benefits of various approaches to treatment.

We conducted a prospective randomized study to compare the results of 3 cycles of epidoxorubicin/docetaxel to 6 cycles of epidoxorubicin/docetaxel prior to surgery in breast cancer patients with clinical stages II and III. Forty-five patients eligible for neoadjuvant chemotherapy were randomly assigned to receive either 3 (group 1) or 6 (group 2) cycles of epidoxorubicin/docetaxel prior to surgery. Chemotherapy consisted of epidoxorubicin 75 mg/m and docetaxel 75 mg/m on day 1 in 3-week cycles. The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the rates of breast-conserving surgery and the axillary lymph node status in both groups. A pCR occurred in 10% (two of 20) in Group 1 and in 36% (nine of 25) in Group 2, which was statistically significant (p=0.045). Breast-conserving surgery could be performed in 70% (14 of 20) in Group 1 and in 76% (19 of 25) in Group 2 (p=0.065). Axillary lymph node status was negative in 45% (nine of 20) in Group 1 and 52% (13 of 25) in Group 2 (p=0.86). We conclude that 6 cycles of pre-operative epidoxorubicin/docetaxel versus 3 cycles of pre-operative epidoxorubicin/docetaxel significantly increases the pCR rates for breast cancer patients.