Background: Among women with unilateral cancer, rates of contralateral prophylactic mastectomy (CPM) are continuing to increase. However, little is known about whether rates and types of complications differ between patients undergoing unilateral mastectomy or bilateral mastectomy, limiting the surgical outcomes evidence that can be presented in pre-surgical decision making for women considering CPM. This study was undertaken to determine whether surgical complications are increased in women undergoing CPM compared to those without CPM. Methods: Between the years 2005–2010, all patients at UCSF undergoing mastectomy with immediate reconstruction were entered into a prospective database. This database was queried for patients with unilateral cancer who had mastectomy and immediate reconstruction with or without CPM. Surgical outcomes, including implant loss, admission for IV antibiotics, and return to OR were evaluated and compared between patients who did and did not undergo CPM. Patients with bilateral cancer or bilateral prophylactic surgery were excluded; analyses were limited to patients with a minimum of 1 year follow-up. Results: 468 patients were identified who met study criteria, totaling 667 breasts. Mean follow-up time was 22 months (range 12 - 69 months). 269 of the 468 (57.5%) patients had unilateral mastectomy only, while 199 of 468 (42.5%) patients also had CPM. There were no differences in tumor grade, stage, follow-up time, smoking history, or radiation (prior or post-surgery) between the two groups. The only significant differences between the unilateral and bilateral groups were median age at diagnosis (50.7 vs. 45.9 respectively; p < .0001) and receipt of neoadjuvant chemotherapy (34.7% vs. 41.3% respectively; p < .01). Surgical outcomes were compared between groups. The overall rate of major complications differed significantly due to an increased rate of infectious complications and unplanned return to surgery in the CPM group (Table 1). Nevertheless, this did not result in a higher implant loss rate in the CPM group. In patients undergoing bilateral mastectomy, overall complication rates were comparable between the index breast and the CPM breast; however, there was a higher implant loss rate in the index breast (22/177 vs. 11/188; p=0.05). Conclusions: While CPM is an increasingly common procedure, it is associated with an increased risk of major post-operative surgical complications. In this cohort, patients undergoing bilateral mastectomy for unilateral cancer had higher rates of overall complications, greater use of IV antibiotics, and more frequent return to the operating room. Since the majority of CPM cases are not at sufficiently high risk for a second breast cancer to meet clinical criteria for prophylactic surgery, guidelines and clinical recommendations should consider these increased complication rates when counseling women contemplating CPM. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD02-01.

BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex skin has become increasingly accepted as an oncologically safe procedure for both prophylactic and therapeutic indications. The goal of this study was to evaluate the oncologic outcomes after TSSM in BRCA mutation carriers. METHODS: We identified 53 BRCA-positive patients who underwent bilateral TSSM for prophylactic (27 patients) or therapeutic (26 patients) indications from 2001 to 2011. Cases were age-matched (for prophylactic cases) or age- and stage-matched (for therapeutic cases) with non-BRCA-positive patients who underwent bilateral TSSM during this time period. Outcomes included tumor involvement of the resected nipple tissue, the development of new breast cancers in patients who underwent bilateral risk-reducing TSSM, and the development of any local-regional recurrence in patients who underwent therapeutic TSSM. RESULTS: Outcomes from 212 TSSM procedures in 53 cases and 53 controls were analyzed. In patients undergoing TSSM for prophylactic indications, in situ cancer was found in 1 (1.9%) of the nipple specimens in the BRCA-positive patients vs. 2 specimens (3.7%) in the non-BRCA-positive cohort (p = 1). At a mean follow-up of 56 months, no new cancers developed in the BRCA-positive or the non-BRCA-positive cohorts. In patients undergoing TSSM for therapeutic indications, in situ or invasive cancer was found in 0 of the nipple specimens in the BRCA-positive patients vs. 2 specimens (3.9%) in the non-BRCA-positive cohort (p = 0.49). At a mean follow-up of 33 months, there were no local-regional recurrences in the BRCA-positive cohort. CONCLUSIONS: TSSM is an oncologically safe procedure in BRCA-positive patients, as is evidenced by the low rates of tumor involvement of the nipple tissue and local-regional recurrence after therapeutic mastectomy. In BRCA-positive patients undergoing TSSM as a risk-reducing strategy, five-year follow-up demonstrates no increased risk for the development of new breast cancers; longer-term follow-up is anticipated to further confirm its safety. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-04.

Background: Neoadjuvant chemotherapy, once reserved for locally advanced breast cancer, has become more common in Stage II disease. While one of its proven benefits is an increase in the frequency of breast conserving surgery, many women will undergo mastectomy despite an excellent clinical response. Indications for post-mastectomy radiation (PMRT) following neoadjuvant therapy are not well defined. Some studies have suggested that certain subgroups of women (young age, triple negative disease) with negative nodes or 1–3 positive nodes after chemotherapy have a significant risk of local-regional failure without PMRT. We conducted a single-institution retrospective study of women undergoing neoadjuvant chemotherapy and mastectomy without PMRT to assess clinical outcomes among this cohort. Methods: 101 women with initial stage I-III disease (20% stage I, 72% stage II, 8% stage III) received neoadjuvant chemotherapy (doxorubicin-based +/− taxane) followed by mastectomy without PMRT between 2005 and 2011. Mean age was 49 years (range 22–81 years). 16% were BRCA+. 66 patients (65%) had clinically negative axillary nodes at presentation, 34% had N1 disease and 1% had N2 disease. Subtype by IHC was 61% luminal A, 11% luminal B (ER+, Her2+), 20% triple negative and 8% ER−, Her2+. At the time of surgery, 81% were node negative and 19% had 1–3 positive nodes. Pathologic complete response (pCR) (breast + axilla) occurred in 28%. Median follow-up was 34 months (range 5.5–84.5 months). Results: There were 2 (2%) local-regional failures (1 axillary recurrence at 52 months after mastectomy and 1 chest wall recurrence at 10 months). Both of these recurrences were in patients with negative nodes and luminal A tumors; patients had 2.2 and 2.5 cm of residual invasive cancer, respectively, and negative margins at mastectomy. There were no local-regional failures in women with triple negative cancers, those with 1–3 positive nodes, or patients younger than 40. Additionally, there were no failures in women with a pCR, including those with initial stage IIIA-B disease. Conclusions: Among carefully selected patients fulfilling low risk criteria for local-regional recurrence, PMRT following neoadjuvant chemotherapy may be omitted without compromising local-regional control. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-07.

INTRODUCTION: Total skin-sparing mastectomy (TSSM) is increasingly offered to women for both therapeutic and prophylactic indications. When combined with immediate breast reconstruction, patients can achieve excellent aesthetic results and high satisfaction. However, the oncologic safety of the procedure remains controversial. Further, the technique can be associated with higher rates of postoperative ischemic complications. We conducted this study to determine oncologic and ischemic outcomes in a large cohort of patients undergoing TSSM and immediate reconstruction. METHODS: Patient and tumor characteristics and treatment details were collected in a prospectively maintained database. All patients undergoing TSSM and immediate breast reconstruction at our institution from 2001 to 2010 were included in the analysis. The development of any post-operative complications or local or distant recurrence was determined. RESULTS: TSSM with immediate reconstruction was performed in 428 patients for a total of 657 breasts. Mean patient age was 46.9 years. 210 patients (49%) had neoadjuvant chemotherapy for locally advanced disease. 114 patients (26.7%) had post-mastectomy radiation therapy. 54% of patients had bilateral mastectomies. Prophylactic mastectomies (either unilateral or bilateral) accounted for 244 (37.1%) of cases, which included bilateral mastectomies in 15 patients (30 cases) who were known BRCA-1 or -2 mutation carriers. Expander-implant reconstruction was performed in 80% of the cases, while the rest of the cases involved autologous reconstruction (15.3%) or immediate implant placement (4.7%). On pathologic examination, nipple tissue from 11 breasts (1.7%) contained in situ cancer and from 9 breasts (1.4%) contained invasive cancer; re-excision was performed in 7 of these cases, the nipple-areolar complex was removed entirely in 9 cases, and radiation therapy was given without further excision in the rest of cases. Ischemic or necrotic post-operative complications included 13 cases (1.9%) of partial nipple loss, 10 cases (1.5%) of complete nipple loss, and 78 cases (11.8%) of skin flap necrosis or incisional dehiscence. At a median follow-up of 23 months (range 3–116 months), 5 patients (1.2%) had developed a local recurrence alone, 10 patients (2.4%) had developed a distant recurrence alone, and 6 patients (1.4%) had developed both loco-regional recurrence and distant metastases. In the subset of patients with at least 3 years’ follow-up, rates of local and of distant recurrence were 1.7% at a median of 45 months follow-up. None of the patients who underwent bilateral prophylactic mastectomy for BRCA-1 or -2 mutations developed subsequent breast cancers. CONCLUSIONS: In this large, high-risk cohort, TSSM was associated with low rates of nipple involvement and loco-regional recurrence. Ischemic complications, although uncommon, often resulted in nipple loss. These short-term outcomes are encouraging, although longer follow-up will be important for confirmation of long-term oncologic safety. Serial improvements in surgical technique can improve selection criteria and reduce post-operative complication rates. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD02-06.