Positive Nipple Margins in Nipple-Sparing Mastectomy: Management of Nipples Containing Cancer or Atypia.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe approach for breast cancer treatment and prevention; however, there are little long-term data to guide management for patients whose nipple margins contain tumor or atypia. METHODS: NSM patients with tumor or atypia in their nipple margin were identified from a prospectively maintained, single-institution database of consecutive NSMs. Patient and tumor characteristics, treatment, recurrence, and survival data were assessed. RESULTS: A total of 3158 NSMs were performed from June 2007 to August 2019. Nipple margins contained tumor in 117 (3.7%) NSMs and atypia only in 164 (5.2%) NSMs. Among 117 nipple margins that contained tumor, 34 (29%) margins contained invasive cancer, 80 (68%) contained ductal carcinoma in situ only, and 3 (3%) contained lymphatic vessel invasion only. Management included nipple-only excision in 67 (57%) breasts, nipple-areola complex excision in 35 (30%) breasts, and no excision in 15 (13%) breasts. Only 23 (24%) excised nipples contained residual tumor. At 67 months median follow-up, there were 2 (1.8%) recurrences in areolar or peri-areolar skin, both in patients with nipple-only excision. Among 164 nipple margins containing only atypia, 154 (94%) nipples were retained. At 60 months median follow-up, no patient with atypia alone had a nipple or areola recurrence. CONCLUSIONS: Nipple excision is effective management for nipple margins containing tumor. No intervention is required for nipple margins containing only atypia. Our results support broad eligibility for NSM with careful nipple margin assessment.

Oncologic Safety of Nipple-Sparing Mastectomy for Breast Cancer in BRCA Gene Mutation Carriers: Outcomes at 70 Months Median Follow-Up.

BACKGROUND: Retention of the nipple-areola complex with nipple-sparing mastectomy (NSM) techniques provides a more natural cosmetic result than procedures that sacrifice the nipple. While the oncologic safety of NSM is established by several studies, there is little long-term data on outcomes in BRCA mutation carriers with breast cancer. PATIENTS AND METHODS: BRCA1/2 mutation carriers who underwent NSM and immediate reconstruction from 2008 to 2019 were reviewed and patients with breast cancer on biopsy or final pathology were included. Patient demographics and tumor characteristics, as well as treatment, recurrence, and survival data were collected. RESULTS: A total of 114 therapeutic NSM were performed in 105 BRCA mutation carriers (56 BRCA1, 47 BRCA2, and two women with both mutations). Median age was 45 years. Cancers were 18% stage 0, 52% stage I, 27% stage II, and 3% stage III. Mean invasive tumor size was 1.6 cm and 33 (35%) invasive tumors were triple negative. There were five (4.4%) positive nipple margins on final pathology; all underwent nipple excision. Most patients (80, 76%) received systemic therapy: 65 (62%) received chemotherapy and 48 (46%) received endocrine therapy. At 70 months median follow-up (range 15-150 months), no patient had developed a recurrence in the retained nipple-areola complex or at the site of a nipple excised for a positive margin. The rate of locoregional recurrence outside the nipple was 2.6%, and the rate of distant recurrence was 3.8%. Overall survival was 96%. CONCLUSIONS: NSM is a safe option for BRCA1 and BRCA2 mutation carriers who undergo mastectomy for breast cancer.

Axillary Recurrence in Sentinel Lymph Node Negative Mastectomy Patients at 16 Years Median Follow Up: Natural History in the Absence of Radiation.

BACKGROUND: Axillary recurrence following lumpectomy with a negative sentinel lymph node biopsy (SLNB) is rare, possibly due to routine use of whole breast radiation. In this study, we characterized the rate of any axillary recurrence among mastectomy patients with a negative SLNB and no adjuvant radiation therapy. METHODS: We identified women who underwent mastectomy with SLNB for early-stage breast cancer (1999-2005) and included patients with pathologically negative nodes and no axillary dissection or adjuvant radiation. The primary outcome was ipsilateral axillary recurrence. RESULTS: A total of 234 women, median age 50 years, underwent 242 mastectomies. Histology showed 112 (46%) invasive cancers, 16 (7%) ductal carcinoma in-situ (DCIS) with microinvasion, and 114 (47%) pure DCIS. Cancers were predominantly estrogen receptor positive (59%) and moderate (41%) or high grade (32%). A mean of 2 final sentinel nodes were excised (range 1-6) and 21 patients (9%) had isolated tumor cells on SLNB pathology. At 16 years median follow up (range 1-22 years), 3 patients (1.2%) developed an isolated axillary failure, and 1 had concurrent axillary and chest wall recurrences (total axillary recurrence rate 1.7%). Three of four axillary recurrences occurred in patients with moderate or high-grade estrogen receptor-positive DCIS without invasion on mastectomy histology. Median time to axillary recurrence was 70.5 months (range 29-132 months). CONCLUSIONS: Axillary recurrence is rare after a negative SLNB, even in the absence of adjuvant radiation. This supports the safety of forgoing additional surgery or radiation to the axilla in the early-stage breast cancer and a negative SLNB.

Analysis of respiratory kinematics: a method to characterize breaths from motion signals.

Objective.Breathing motion (respiratory kinematics) can be characterized by the interval and depth of each breath, and by magnitude-synchrony relationships between locations. Such characteristics and their breath-by-breath variability might be useful indicators of respiratory health. To enable breath-by-breath characterization of respiratory kinematics, we developed a method to detect breaths using motion sensors.Approach.In 34 volunteers who underwent maximal exercise testing, we used 8 motion sensors to record upper rib, lower rib and abdominal kinematics at 3 exercise stages (rest, lactate threshold and exhaustion). We recorded volumetric air flow signals using clinical exercise laboratory equipment and synchronized them with kinematic signals. Using instantaneous phase landmarks from the analytic representation of kinematic and flow signals, we identified individual breaths and derived respiratory rate (RR) signals at 1 Hz. To evaluate the fidelity of kinematics-derived RR, we calculated bias, limits of agreement, and cross-correlation coefficients (CCC) relative to flow-derived RR. To identify coupling between kinematics and flow, we calculated the Shannon entropy of the relative frequency with which flow landmarks were distributed over the phase of the kinematic cycle.Main Results.We found good agreement in the kinematics-derived and flow-derived RR signals [bias (95% limit of agreement) = 0.1 (± 7) breaths/minute; CCC median (IQR) = 0.80 (0.48-0.91)]. In individual signals, kinematics and flow were well-coupled (entropy 0.9-1.4 across sensors), but the relationship varied within (by exercise stage) and between individuals. The final result was that the flow landmarks did not consistently localize to any particular phase of the kinematic signals (entropy 2.2-3.0 across sensors).Significance.The Analysis of Respiratory Kinematics method can yield highly resolved respiratory rate signals by separating individual breaths. This method will facilitate characterization of clinically significant breathing motion patterns on a breath-by-breath basis. The relationship between respiratory kinematics and flow is much more complex than expected, varying between and within individuals.