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The Changing Field of Locoregional Treatment for Breast Cancer

The Changing Field of Locoregional Treatment for Breast Cancer

The change to less-morbid local therapy for operable breast cancer continues. Systemic induction therapy, whether hormonal therapy or chemotherapy, increases the eligibility for breast-conserving surgery. Sentinel lymph node biopsy (SLNB) has greatly reduced the requirement for axillary dissection, and recent data show that, in addition, whole-breast irradiation can obviate the need for dissection in most patients with clinically node-negative, SLN-positive disease. Although resection margins must be negative for best results, there is no clear evidence that margins exceeding "no ink on tumor" for invasive cancer, or 2 mm for ductal carcinoma in situ, are significantly better. The role of radiation has been clarified, with a clear survival advantage for patients with node-positive disease; however, hypofractionation, which permits a briefer period of treatment, and accelerated partial breast irradiation (APBI) show promise of even further reductions in treatment—although late results for APBI are still needed. Elderly patients (> 70 years) with node-negative disease and estrogen receptor–positive tumors who have been treated with hormonal therapy can avoid primary breast irradiation without significant risk of ultimate breast loss or inferior survival.

Since 1990, death rates from breast cancer have decreased, mainly in women younger than 50 years of age (3.3% per year) vs women aged 50 years or older (2% per year), reflecting the benefit of widespread use of systemic treatment added to early detection.[1]

Improved local control is also causally associated with improved breast cancer survival. An absolute reduction in local recurrence at 5 years is associated in a 4:1 ratio with an absolute survival advantage at 15 years in the overviews of clinical trials.[2] Guidelines for locoregional treatment of breast cancer were first published by the US National Institutes of Health in 1991.[3] Since then, new surgical and radiotherapeutic techniques have been developed, and revised guidelines for locoregional management were suggested in 2008 by the Biedenkopf Expert Panel Members.[4]

Over the past 50 years there have been major changes in the treatment of patients with breast cancer, with "less is more" being the theme. Treatment of breast cancer has evolved dramatically from the Halsted radical mastectomy, and many women now choose breast-conserving surgery and sentinel node biopsy. Breast-conserving surgery (BCS) is defined as the complete removal of the tumor with a concentric margin of surrounding healthy tissue and maintenance of acceptable cosmesis. BCS should be followed by radiation therapy to achieve an acceptably low rate of local recurrence.

Neoadjuvant Chemotherapy

In an effort to increase the number of patients eligible for breast conservation, neoadjuvant chemotherapy that shrinks the primary tumor before surgery has become an appealing option.[5] In a large randomized trial, National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-18, investigators randomized 1,523 women with Stage I–IIIa breast cancer to receive doxorubicin (Adriamycin, A) and cyclophosphamide (C) either preoperatively or postoperatively.[6] A reduction in tumor diameter of at least 50% was noted clinically in 80% of the patients, and in 37% no tumor was clinically apparent after chemotherapy. The initial findings of the study were reported at 5 years[7]; in the 9-year follow-up publication,[6] there continued to be no difference in overall survival or disease-free survival in patients receiving chemotherapy preoperatively vs postoperatively. The breast conservation rate was 68% for the neoadjuvant arm and 60% for the adjuvant arm. The reduction in tumor volume allows an improved cosmetic outcome in the majority of patients. Induction chemotherapy followed by BCS and radiation therapy is safe and increases the eligibility for breast preservation in approximately one-fourth of patients with large tumors relative to breast size. From a surgical standpoint, when the neoadjuvant approach is being considered, it is mandatory to insert a radioopaque marker into the tumor in order to localize the surgical site after partial or complete tumor regression.

Another important advantage of neoadjuvant chemotherapy is that it probes the chemosensitivity of the tumor, providing information of great importance in terms of development of systemic treatments for chemoresistant tumors. Tumors exhibiting the characteristics referred to as luminal A (strongly ER-positive, PR-positive, HER2-negative) exhibit less-dramatic reductions in volume with neoadjuvant chemotherapy but will often respond to neoadjuvant therapy with aromatase inhibitors or tamoxifen. Conversely, for HER2-positive tumors, adding trastuzumab (Herceptin) to a standard neoadjuvant regimen achieved a pathologic complete response (pCR) of 65.2%, compared with a 26% pCR in patients who did not receive trastuzumab.[8]

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