Incidence of breast cancer recurrence in the nipple-areola complex (NAC) following nipple-sparing mastectomy (NSM) and immediate breast reconstruction was extremely limited over the long term, Korean investigators found, and cancers that did recur did not increase risk of distant metastases or compromise overall survival. With median follow-up of 85 months (range 14-185 months), 4.1% of 962 breasts from 944 patients developed cancer recurrence at the NAC as the first event after NSM, BeomSeok Ko, MD, PhD, of the University of Ulsan in Seoul, and colleagues reported in JAMA Surgery. The researchers found 5-year cumulative recurrence rates of 3.5% at the NAC and 3.4% at other sites. Factors identified as increasing the risk of having cancer recur at the NAC included multifocal or multicentric disease, hormone receptor-negative and HER2-positive status, high histologic grade, and an extensive intraductal component in the primary tumor. "The main concern associated with nipple-sparing mastectomy (NSM) is the risk of local breast cancer recurrence at the retained nipple-areola complex (NAC) consequent to occult nipple involvement," Ko and colleagues wrote. "As more patients with breast cancer undergo NSM, these data may be useful in estimating a prognosis for cancer recurrence at the NAC and guiding management decisions," they concluded. Patients with a clinically normal NAC and no skin involvement were offered the option of NSM. Median age at diagnosis was 43 (range 23-67 years), and 52.8% received adjuvant chemotherapy. About 80% also received adjuvant hormonal therapy and 10% received adjuvant radiotherapy. The median time between cancer recurrence at the NAC and the primary surgery was 35 months (range 7-135 months). In multivariate analysis, the presence of an extensive intraductal component in the primary tumor had the strongest association with cancer recurrence at the NAC, at a hazard ratio of 3.33 (95% CI 1.26-8.82, P=0.02). This was followed closely by multifocality or multicentricity of the breast cancer (HR 3.30, 95% CI 1.50-7.29, P=0.003), hormone receptor-negative as well as HER2- or HER2/neu-positive status (HR 3.05, 95% CI 1.19-7.79, P=0.02), and high histologic grade (HR 2.64, 95% CI 1.13-6.16, P=0.03). All patients who developed a recurrence at the NAC underwent wide local excision. At 10 years, distant metastasis-free survival rates were 89.3% in those patients versus 94.3% for patients without recurrence. Overall 10-year survival was 100% in patients with recurrence and 94.5% in those without. Limitations of the study included the fact that it was a phase II study design with all its inherent pitfalls. Not for all Patients As the authors pointed out, NSM followed by immediate breast reconstruction has the advantage of providing excellent aesthetic results without compromising short-term oncologic safety. Consequently, the procedure is gaining in acceptance, but long-term outcomes have been largely unknown. "To our knowledge, the current study was the first to focus specifically on the incidence of and risk factors associated with cancer recurrence at the NAC as the first event after NSM in a large series of patients with invasive breast cancer in a long-term follow-up period (>5 years)," Ko and colleagues pointed out. Sarah Cate, MD, of the Icahn School of Medicine at Mount Sinai in New York, who was not involved with the study, told MedPage Today that the study is not practice-changing as it dovetails with what surgeons already believe about NSM. "However, it has to be done in the appropriate patient," she stressed. For surgeons who offer NSM in the U.S., "appropriate patients" are those without multifocal (multiple tumors within the same breast quadrant) or multicentric disease (tumors in multiple quadrants). NSM also wouldn't be appropriate for patients with an extensive intraductal component in their primary tumor or those with tumors bigger than 3 cm. And NSM is appropriate only when the tumor is at least 2 cm away from the NAC, Cate said. In contrast, women with hormone receptor-negative tumors would not be considered at increased risk for cancer recurrence at the NAC in the U.S., Cate said, so this particular risk factor does not enter into a surgeon's choice to do this procedure or not. As the report didn't make clear whether the Korean surgeons had followed current guidelines, Cate added, it could be that they were offering NSM to women whose tumors were closer to the NAC area than the recommended 2 cm, which might explain why the incidence of breast cancer recurrence at the NAC, while low in the study, was still higher than reported in other series, where recurrences are more likely to develop in different parts of the breast. Source
