Team Approach to Nipple-Sparing Mastectomy

Allen Gabriel

Maurice Y. Nahabedian

Toni Storm

G. Patrick Maxwell

History

Surgical management of breast cancer has evolved in the past 50 years toward a more minimally invasive approach with better aesthetic outcomes, but without compromising oncologic safety. With the realization of the contribution of the quality of the mastectomy skin envelope to aesthetic outcome, mastectomy techniques have evolved from radical mastectomies where all of the breast tissue, including the skin, nipple, and areola, as well as the axillary lymph nodes are removed to skin-sparing mastectomies (SSMs) where breast tissue, including the nipple areolar complex (NAC), are removed but the breast skin is preserved as much as possible to nipple-sparing mastectomies (NSMs), which is a SSM with preservation of the NAC.

Preserving the NAC has aesthetic benefits as immediate breast reconstruction following NSM allows for better cosmetic results compared with other forms of mastectomy (1). The nipple is a key defining visual feature of the breast and is the point at which the most natural convexity of the breast occurs. Although staged nipple reconstruction and areola tattooing can potentially achieve similar aesthetic results, they are often short-lived as loss of projection and fading, respectively, is common over time (2). NSM aims to create an aesthetic result that is closer to the natural state than breast reconstruction techniques.

Preserving the NAC is also associated with improved patient satisfaction, psychological benefit, and quality of life after breast reconstruction compared with non-NSMs (3). All postmastectomy patients are fraught with distress brought on by the diagnosis of breast cancer and suffer a severe alteration of body image and the resultant adverse psychological consequences (4,5). Preservation of the NAC can be an extremely vital part of their rehabilitation in the sense that it visually transforms the mastectomy skin into a breast immediately following breast reconstruction.

NSM was attempted in the 1980s as a treatment for breast cancer (6) but never gained popularity due to the controversies surrounding oncologic safety, which persist to this day. However, better tumor detecting technologies are creating support for the return of this concept in recent years in the therapeutic setting. In the risk-reducing setting, NSM has become a well-established practice (7).

Risk-Reduction NSM

NSM was first described in the 1960s for breast cancer risk reduction in patients with benign breast lesions (8). The concept did not gain popularity because the outcomes were inconsistent and unimpressive, the complication rate was high, and most importantly efficacy in risk reduction could not be demonstrated because of a lack of selection criteria. Thirty years later, the seminal work of Hartmann changed the perception of risk-reduction NSM. In women with a family history of breast cancer, prophylactic NSM was demonstrated to be associated with a reduction in the incidence of breast cancer of at least 90% (9). Subsequently, the efficacy of NSM was demonstrated in patients with BRCA1 and BRCA2 gene mutations where a 90% to 100% risk reduction was reported (10). Similarly, in women with a personal and family history of breast cancer, contralateral prophylactic mastectomy was shown to result in a 94% risk reduction in premenopausal women and a 96% risk reduction in postmenopausal women (11).

The indications for risk-reducing NSM have evolved over the past 25 years. Initially, NSM was primarily indicated in women with a strong family history and/or a personal history of high-risk breast lesions such as lobular carcinoma in situ or atypical hyperplasia (9). In more recent time periods, the indications have shifted to primarily those with genetic mutations (12). However, NSM can be considered virtually in all prophylactic cases after ruling out malignancy and discussing with patients all risk-reducing strategies. Preoperative evaluation for NSM should include complete imaging studies, preferentially breast magnetic resonance imaging (MRI).

Therapeutic NSM

Increasing Trends of NSM

In carefully selected patients, NSM as a treatment for breast cancer has been increasingly performed in the
last decade. A recent analysis of the National Cancer Database indicates an 800-fold increase in NSM among women who underwent treatment for stage 0–III breast cancer followed by reconstruction from 2005 to 2015 (from 1.7% to 14.3%) (13). By 2015, NSM was performed in 15.3% of mastectomies with reconstruction for ductal carcinoma in situ (DCIS), 14.3% of mastectomies with reconstruction for stage I–II breast cancer, and 10.7% of mastectomies with reconstruction for stage III breast cancer.

Oncologic Safety of NSM

Current evidence suggests that in appropriately selected patients, NSM is associated with an acceptable rate of locoregional cancer recurrence. Recent systematic reviews of published studies place the recurrence rate at 1.8% to 2.3% (14,15,16). The recurrence rate with NSM has been shown to be comparable to conventional mastectomy (17,18,19), breast-conserving surgery (20), and SSM (21). Despite the acceptable recurrence rate, concerns still exist that occult malignancy could remain within residual glandular breast tissue left behind underneath the skin envelope (7). According to the SKINI-trial, residual breast tissue is commonly observed after SSM and NSM, in about half of the cases (22). However, invasive or in situ carcinomas are rarely found in the skin envelope. In the SKINI-trial, 99 SSM and 61 NSM were performed. Of biopsies from the skin envelope (10 biopsies per SSM, 14 biopsies per NSM), residual disease was detected in 3 biopsies.

Oncologic Indications/Contraindications for NSM

The indications for therapeutic NSM have evolved and expanded over time, thus, allowing a wider population of patients to benefit from this procedure. Previous oncologic criteria for NSM included tumor size <3 cm, tumor-to-nipple distance >2 cm, clinically negative axillary nodes, no skin involvement or inflammatory cancer, and possible preoperative MRI to exclude nipple involvement (23). These criteria were based on published studies at that time that investigated the relationships between oncologic parameters and nipple involvement. A systematic review of these studies, has summarized the significant findings (15). Essentially, reduced tumor-to-nipple distance, lymph node metastasis, lymphovascular invasion, HER-2 positivity, grade 3 tumor, multicentricity, and retroareolar location were found to increase the incidence of occult nipple malignancy. In addition, the four most common tumor types (invasive ductal carcinoma, invasive lobular carcinoma, DCIS, invasive ductal carcinoma/DCIS) were found to have similar nipple involvement rates, ranging from 15% to 17%.

Currently, nipple involvement, inflammatory breast cancer, skin involvement, and bloody nipple discharge (but not clear nipple discharge) are absolute contraindications for NSM (7). Tumor size and tumor-to-nipple distance no longer factor as oncologic criteria but rather the primary focus has shifted to nipple margin status. Because a negative retroareolar margin may exclude occult nipple involvement with a high negative predictive value even in patients at high risk of occult nipple involvement before surgery, such as patients with a tumor nipple distance ≤1 cm or tumors >3 cm in diameter (24), thus, the current strategy of treating the nipple margin like any other margin. While clinical signs of nipple involvement and R1 resection at the nipple margin have traditionally been considered to be contraindications to nipple preservation (25), the clinical relevance of a positive retroareolar margin in an individual patient is, however, unknown (7). Moreover, while a positive retroareolar margin would require the excision of the nipple, there is no clear consensus on whether the areolar can be preserved. Areolar involvement is of low occurrence even in the presence of nipple involvement. This was shown in a retrospective study of 217 mastectomy patients where nipple involvement was seen in 10.6% of patients and areolar involvement in 0.9% of patients (26). It should be noted that on rare occasions nipple involvement can occur as a late event after NSM. A retrospective study of 861 patients reported 7 cases of local recurrence in the nipple on an average of 32 months after surgery. NAC was completely removed in all cases and no further recurrences were noted at an average follow-up of 47.4 months (27).

Inflammatory breast cancer is an absolute contraindication for skin sparing even after neoadjuvant chemotherapy and complete remission of all skin changes (7). This is because at diagnosis, inflammatory breast cancer is always at a locally advanced stage (at least stage III) as breast cancer cells have grown into the skin. Further, even without redness, edema of the skin with enhancement on imaging is also a contraindication to skin sparing.

While skin involvement is an absolute contraindication, opinion varies regarding whether cT4b and cT4c breast cancers limited to a 1 × 1 cm area of skin ulceration should be a contraindication to skin preservation. In addition, there is no clear consensus on whether the absence of any distance between tumor and skin on preoperative imaging, even in the absence of clinical signs of skin infiltration, or a histologic margin of less than 1 mm should be contraindications to skin preservation.

NSM and Breast Irradiation

Premastectomy breast irradiation was once considered to be a contraindication to NSM because of concerns of nipple ischemia from a compromised bloody supply to the breast. Further, irradiation also has deleterious effects on the skin eventually leading to skin fibrosis. A recent retrospective analysis of 605 NSMs (517 no radiation, 43 premastectomy radiation, and 45 postmastectomy radiation) followed by immediate reconstruction, however,
reported a nipple retention rate of 90% in patients who had radiation therapy (pre- or postmastectomy). Nipple removal secondary to malposition or positive oncologic margins in patients with radiation did not differ significantly from those without radiation (28). In another retrospective analysis of 982 NSMs, 816 with no radiation, 67 with preoperative radiation, and 97 with postmastectomy radiation, experienced nipple loss at 0.9%, 4.3%, and 4.1%, respectively. Although nipple loss was significantly higher in irradiated breasts, the retention rate was greater than 95% (29). Both these studies demonstrate that NSM can be successfully performed in the setting of breast irradiation.

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