Expanded Indications for Nipple-Sparing Mastectomy and Immediate Breast Reconstruction in Patients Older Than 60 Years.

INTRODUCTION: Although nipple-sparing mastectomy (NSM) and immediate breast reconstruction (IBR) have long been praised for excellent cosmetic results and the resultant psychosocial benefits, the feasibility and safety of these procedures in patients older than 60 years have yet to be demonstrated in a large population. METHODS: Patients undergoing NSM with or without IBR at the MedStar Georgetown University Hospital between 1998 and 2017 were included. Patient demographics, surgical intervention, and complication and recurrence events were retrieved from electronic medical records. Primary outcomes were recurrence and complication rates by age groups older and younger than 60 years. RESULTS: There were 673 breasts from 397 patients; 58 (8.6%) older than 60 years and 615 (91.4%) younger than 60 years with mean follow-up of 5.43 (0.12) years. The mean age for those older than 60 was 63.9 (3.3) years, whereas that for those younger than 60 was 43.1 (7.9) years (P < 0.001). The older than 60 group had significantly higher prevalence of diabetes, rates of therapeutic (vs prophylactic) and unilateral (vs bilateral) NSM, and mastectomy weight. However, there were no significant differences by age group in complication rates or increased risk of locoregional or distant recurrence with age. CONCLUSIONS: Based on similar complication profiles in both age groups, we demonstrate safety and feasibility of both NSM and IBR in the aging population. Despite increased age and comorbidity status, appropriately selected older women were able to achieve similar outcomes to younger women undergoing NSM with or without IBR.

Nipple-Sparing Mastectomy With Immediate Reconstruction After Breast-Conserving Therapy and Radiation: Complications and Oncologic Safety.

INTRODUCTION: Nipple-sparing mastectomy (NSM) offers improved, patient-centered outcomes with demonstrated oncologic safety ( Ann Surg Oncol 2020;27:344-351). Indications for NSM continue to expand to patients outside of the traditional eligibility criteria, including those with prior breast-conserving therapy (BCT) with radiotherapy. Currently, limited data exist evaluating both short- and long-term outcomes in patients proceeding to NSM after prior BCT. METHODS: All patients undergoing bilateral NSM in a single institution from 2002 through 2017 with history of prior BCT were included in the final cohort, without exclusions. A retrospective chart review was performed to identify patient demographics, operative details, and complications. Outcomes assessed included early complications (<30 days from NSM), late complications (>30 days), rates of prosthetic failure, unplanned reoperations, and reconstructive failures, as well as oncologic safety. Student t , χ 2 , and Fisher exact tests were used to analyze outcomes of paired (BCT vs non-BCT) breasts within each patient. RESULTS: A total of 17 patients undergoing 34 NSMs were included. Each had a history of BCT and either ipsilateral breast recurrence (64.7%), risk-reducing NSM (23.5%), or a new contralateral primary cancer (11.8%). The cohort had a mean age of 51.1 years. With regard to acute complications (ischemia, infection, nipple-areolar complex or flap ischemia or necrosis, and wound dehiscence), there was no significant difference noted between breasts with prior BCT versus no prior BCT overall (41.2% vs 35.3%, respectively; P = 0.724). Complications occurring after 30 days postoperatively (capsular contracture, contour abnormality, animation deformity, bottoming out, rotation, and rippling) in prior BCT breasts versus no prior BCT had no significant differences overall (58.8% vs 41.2% respectively; P = 0.303). The mean follow-up was 5.5 years, during which no patients had a reported locoregional or distant recurrence in either breast. CONCLUSIONS: No significant differences in early or late complications were identified between breasts in patients undergoing bilateral NSM with a history of unilateral BCT and XRT. In the 5.5 years of follow-up, there were no recurrences, lending support to NSM for management of recurrent disease in addition to National Comprehensive Cancer Network-recommended total mastectomy. We propose that NSM should not be contraindicated in patients exposed to radiation with BCT.

A Critical Appraisal of Late Complications of Prepectoral versus Subpectoral Breast Reconstruction Following Nipple-Sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) offers improved aesthetics without compromising oncologic safety. Subpectoral breast reconstruction has long been standard practice, although prepectoral reconstruction has recently resurged in popularity. Due to this recent paradigm shift, studies comparing long-term outcomes by reconstructive plane are lacking. METHODS: A retrospective review was conducted on consecutive NSMs with implant-based reconstruction in either the prepectoral or subpectoral plane from 2014 to 2018. Patient demographics, implant specifications, and operative details were collected to evaluate primary outcomes of prosthetic failure and unplanned reoperations by reconstructive plane. Secondary outcomes included animation deformity, capsular contracture, rippling, plane change, and minor revisions, including fat grafting. Bivariate and multivariate analyses were performed to assess outcomes. RESULTS: Overall, 405 NSMs were performed on 228 women (subpectoral = 202, prepectoral = 203), with a mean follow-up of 2.1 years (standard deviation 1.1). During the study period (2014-2018), a shift from subpectoral to predominantly prepectoral mastectomies occurred in 2017. Prepectoral reconstructions were more often direct-to-implant (DTI) compared with subpectoral (73.9% vs. 33.2%, p < 0.001). Prepectoral reconstruction demonstrated significantly reduced prosthetic failure (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.14-0.65) and unplanned reoperations (OR 0.43, 95% CI 0.24-0.77) compared with subpectoral reconstruction after controlling for implant characteristics and other possible confounders. Prepectoral patients experienced decreased animation deformity overall (19.7% vs. 0.0%, p < 0.001), with plane changes seen in 10.6% of subpectoral reconstructions for animation deformity correction. Prepectoral patients experienced an increase in rippling (15.3% vs. 6.1%, p = 0.003) without a significant increase in fat grafting (subpectoral = 11.6% vs. prepectoral = 12.3%, p = 0.829). CONCLUSIONS: This single-institution experience compares late complications of prepectoral and subpectoral implant-based reconstruction following NSM. Prepectoral reconstruction can be safely performed with improved understanding of mastectomy planes, readily affords DTI reconstruction, and reduces animation deformity at the expense of rippling.

Critical evaluation of factors contributing to time to mastectomy within a single health care system.

Increased time to mastectomy (TTM) has significant implications for mortality, well-being, and satisfaction. However, certain populations are subject to disparities that increase TTM. This study examines vulnerable populations and the patient-, disease-, provider-, and system-level factors related to treatment delays. Patients undergoing mastectomy for breast cancer from 2014 to 2018 across 8 hospitals in a single health care system were retrospectively reviewed. Demographics, disease characteristics, and provider- and system-level information were collected. Time from biopsy-proven diagnosis to mastectomy was calculated. Univariate analysis identified variables for inclusion in the multivariable model. One thousand, three hundred thirty patients met inclusion. Median TTM was 55.0 days. Factors from all levels-patient, disease, provider, and systemic-were significantly related to disparities. African-American patients had 11.6% longer TTM compared to white patients (69.0 vs 56.0 days, P < .0001). TTM was 15.5% longer for low-income patients when compared to high-income patients (65.0 vs 49.0 days, P = .0014). Preoperative plastic surgery visits led to 19.3% longer TTM (P = .0012); oncologic appointments for neo-adjuvant chemotherapy led to a 231.0% increase (P < .0001). Average time from last neo-adjuvant treatment to mastectomy was 44.4 days (SD 26.5); average TTM from diagnosis for patients not receiving neo-adjuvant chemotherapy was 58.5 days (SD 13.3). Patients with Medicaid waited 14.5% longer compared to patients with commercial insurance (94.0 vs 62.0 days, P = .0005). In our review of care across a large health care system, we identified multiple levels contributing to disparities in TTM. Identification of these disparities offers valuable insight into process improvement and intervention.

Opioid-free anesthesia for patients undergoing mastectomy: A matched comparison.

Opioid-free anesthesia (OFA) is being implemented in breast surgery due to increased awareness of adverse effects and the national opioid crisis. The objective of this study was to examine the effect of OFA on postoperative pain and postoperative nausea and vomiting (PONV) in mastectomy patients. A single-institution matched-cohort study was conducted from 2014 to 2017 on 48 women undergoing mastectomy, with the majority also undergoing immediate prosthetic-based reconstruction. Patients received either conventional anesthesia (CA) or a novel OFA regimen. Primary outcomes included postoperative pain scores, opioid use, and need for antiemetics that were evaluated both in the PACU and on the hospital floors. No significant differences were found in PACU opioid or antiemetic use between OFA and CA. Pain scores in PACU and on POD0 were not significantly different. There was a significant but modest decrease on POD1 in OFA patients (3.9 vs. 5.1, P = .046). Additionally, patients with higher intraoperative opioid regimens experienced significantly increased PONV (P = .023). This study demonstrated the efficacy of OFA in controlling postoperative pain and nausea compared to a traditional opioid-based regimen. Regardless of intraoperative opioids, patients experienced similar postoperative opioid requirements and PONV with decreased pain scores. Thus, OFA is feasible in mastectomy patients and should be further evaluated in select patients.

Neoadjuvant Chemotherapy and Nipple-Sparing Mastectomy: Timing and Postoperative Complications.

BACKGROUND: As the demand for nipple-sparing mastectomy (NSM) increases and surgeons expand the eligibility criteria, a subset of patients may become candidates following neoadjuvant chemotherapy (NACT). However, the impact of NACT on postoperative complications remains unclear as the current literature is discordant. METHODS: A single-institution, retrospective chart review was performed on patients undergoing NSM from 1989 to 2017. Patient demographics, surgical intervention, systemic treatment, and complication rates were collected. Primary outcomes were 30-day postoperative complications, including nipple-areolar necrosis, skin flap necrosis, infection, wound dehiscence, hematoma, and seroma. Secondary outcomes included characterization of the timing between chemotherapy and surgical intervention, and the impact on complication rates. Each breast was considered independently for analysis, and breasts undergoing either NACT or primary surgery (PS) were compared. RESULTS: Of the 832 breasts included, 88 (10.6%) received NACT and 744 (89.4%) underwent PS. Baseline complication rates were not significantly different between the NACT group and the PS group (5.7% vs. 10.6%; p = 0.119). When controlling for age, body mass index (BMI), smoking, and prior radiation, NACT was not a predictor of complications. Time from completion of NACT to PS occurred at a median of 40.5 days (interquartile range 31.3-55.3), and decreased intervals were not associated with increased complication rates. CONCLUSIONS: Postoperative complications following NSM in patients completing NACT are comparable with those receiving PS. Patients undergoing NACT do not have a significantly increased risk of necrosis, unintended reoperations, or nipple loss. NACT should not be considered a contraindication for NSM.

Positive Nipple Margin After Nipple-Sparing Mastectomy: An Alternative and Oncologically Safe Approach to Preserving the Nipple-Areolar Complex.

BACKGROUND: The aim of this study is to describe a less aggressive approach to management of positive nipple margin following nipple-sparing mastectomy (NSM), allowing for preservation of the nipple-areolar complex (NAC). STUDY DESIGN: A single-institution retrospective chart review was performed for patients undergoing NSM from 1989 to 2017. Positive nipple margin was defined as any residual invasive carcinoma or ductal carcinoma in situ (DCIS) within the additional nipple margin. Management included complete NAC removal, subareolar shave biopsy, or observation alone. Primary outcomes included rates of positive nipple margin and local recurrence. RESULTS: A total of 819 breasts underwent NSM, yielding a total of 32 breasts (3.9%) with positive nipple margin. Management included 11 (34.4%) subareolar shave biopsies, 15 (46.9%) complete NAC excisions, and 5 (15.6%) with observation alone, plus 1 (3.1%) lost to follow-up. Final pathology after subareolar shave biopsy did not reveal any residual disease, and no patients developed NAC necrosis or required NAC removal. Final pathology after NAC excision revealed 3 of 15 with additional disease (1 invasive ductal carcinoma, 2 DCIS). Of the five patients who had no subsequent intervention, tumor pathology was DCIS in all cases. One patient received adjuvant radiation therapy. Mean time to intervention was 3.7 ± 1.9 with mean follow-up of 2.9 years. CONCLUSIONS: Management of positive nipple margin after NSM with subareolar shave biopsy is a safe alternative to preserve the NAC.

Timing of radiation therapy in nipple-sparing mastectomy influences outcomes and patient-reported quality of life.

The aim of this study is to assess the complication profile and impact on patient-reported quality of life in those undergoing nipple-sparing mastectomy (NSM) with immediate breast reconstruction and subsequent prosthetic reconstruction in patients with prior breast radiation therapy (pRT) vs those receiving adjuvant post-mastectomy radiation therapy (PMRT). An IRB-approved, retrospective analysis was performed from 2002 to 2014 to identify NSM patients that underwent pRT or PMRT. A 22-item Likert scale questionnaire was administered by a third party to register patient-reported quality of life. Forty patients met criteria for outcomes analysis, and 30 patients answered the questionnaire. Mean age was 45.6 years old and mean follow-up was 3.8 years. Complication rates for the PMRT cohort were 61.9% vs 31.6% in the pRT cohort, P = .067, and those requiring operative intervention were PMRT 38.1% vs pRT 5.3%, P = .021. Nipple-areolar complex survival was 100% in the pRT vs 85.7% in the PMRT, P = .233. Breast-related quality of life scores were superior in the pRT group within multiple domains. Patients are more likely to develop complications requiring an operative intervention and have decreased breast-related quality of life when undergoing NSM with PMRT compared to patients undergoing NSM having received pRT.

TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer.

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.

Literature review and guide for optimal position in implant-based breast reconstruction.

Background and Objective: Identification of ideal candidates for prepectoral versus retropectoral implant-based breast reconstruction relies on careful preoperative risk assessment and intraoperative flap evaluation. Few guidelines exist to guide the surgeon's decision-making process when evaluating the preferred plane for implant placement. Methods: A literature review was performed to develop clinical decision-making algorithms for direct-to-implant (DTI) reconstruction with acellular dermal matrix (ADM) for patients undergoing prophylactic or therapeutic nipple-sparing mastectomy (NSM) based on patient characteristics, surgical techniques, and outcomes. Key Content and Findings: Prepectoral reconstruction is most suitable for patients with small breasts or macromastia with desire for breast reduction, low-grade ptosis, smaller implant sizes, those undergoing PMRT, and for those who aim to mitigate animation deformity and capsular contracture. Retropectoral reconstruction may be recommended for patients with larger breasts with no desire for size change requiring additional prosthesis support, and in patients who aim to reduce likelihood of rippling and need for subsequent fat grafting procedures to address contour abnormalities. Conclusions: Careful preoperative and intraoperative assessment of reconstruction options for patients undergoing implant-based breast reconstruction is necessary to mitigate complications and produce superior aesthetic outcomes. Decision algorithms may be used to determine ideal surgical techniques based on patient factors, like radiation history and planning, breast size and ptosis, and patient preferences.

Review of Autologous Fat Grafting in Postmastectomy Reconstruction Patients: Nonroutine Diagnostics and Oncologic Safety.

Autologous fat grafting (FG) is increasingly used as an adjunctive reconstruction technique to augment volume, achieve symmetry, and improve contour deformities. This study aims to characterize the oncologic and surgical safety of FG in women undergoing autologous breast reconstruction (ABR) or implant-based reconstruction (IBR). Methods: A retrospective chart review was performed for all patients undergoing FG at a multi-site single health system between 2015 to 2018. A total of 228 eligible breasts from 155 patients were identified using Current Procedural Terminology codes. Patients were divided by reconstructive technique. Bivariate analyses compared baseline characteristics and post-FG outcomes. Results: Mean age for patients undergoing ABR (129 breasts) was 52.8 years compared to 48.6 years for those undergoing IBR (99 breasts; P = 0.002). A heavier volume of fat was grafted per ABR breast (143.8mL) than per IBR breast (102.2mL; P = 0.002). Forty-seven (20.6%) breasts required FG revision, more frequently in ABR breasts (31.0%) than IBR breasts (7.1%; P < 0.001). Following FG, 17.5% of patients experienced a palpable mass, and 18.9% of breasts underwent nonroutine diagnostics or procedures, with no difference between ABR and IBR groups. Most biopsies noted benign findings such as fat necrosis (2.2%) or a benign mass (0.9%), with recurrence only noted in two patients (0.9%). Mean follow-up was 20.4 months. Conclusion: FG is a safe, surgically simple procedure more commonly performed in ABR breasts. FG use in ABR and IBR breasts is oncologically safe, with no impairment in breast surveillance and low rates of locoregional recurrence, but possibly increased incidence of nonroutine imaging and biopsies.

Decreased postoperative pain and opioid use following prepectoral versus subpectoral breast reconstruction after mastectomy: A retrospective cohort study: Pain after pre- versus subpectoral reconstruction.

BACKGROUND: Prepectoral (PP) breast reconstruction is now commonly performed and minimizes dissection of the pectoralis major muscle. Data are lacking comparing the immediate postoperative recovery of these patients as compared with traditional subpectoral (SP) breast reconstruction. METHODS: From December 2015 to February 2017, 73 patients underwent PP prosthetic-based reconstruction at a single academic institution. PP cases were matched 1:1, by age and stage, to patients undergoing traditional SP reconstruction. Analysis of postoperative pain (visual analog scale) and opioid use (oral morphine equivalents, OME), was performed with both bi- and multivariate analyses. Additional outcomes explored included length of stay (LOS) and reconstructive intervention by plane of prosthetic reconstruction. RESULTS: A total of 146 patients were included in the final cohort. PP reconstruction was associated with higher rates of direct-to-implant reconstruction (84.9% vs. 34.3%, p <0.001) and higher rates of initial prosthetic fill (401.53 mL vs. 280.88 mL, p<0.001). Patients undergoing PP reconstruction had significantly reduced postoperative pain (4.29 vs. 5.44, p<0.001) and in-hospital opioid use (62.63 mg OME vs. 98.84 mg OME, p = 0.03) compared with SP patients. This result remained in multivariate analysis for both pain (3.94 vs. 5.25, p<0.001) and opioid use (17.14 mg OME vs. 63.03 mg OME, p = 0.03). Additionally, patients undergoing PP reconstruction had significantly reduced overall LOS on multivariate analysis (21.36 vs. 26.28 h, p = 0.02). CONCLUSION: Following mastectomy, PP breast reconstruction results in significantly reduced pain, opioid use, and hospital LOS compared with SP reconstruction.

Acute Postoperative Complications in Prepectoral versus Subpectoral Reconstruction following Nipple-Sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy is associated with improved aesthetics and oncologic safety. Recently, there has been a resurgence in prepectoral reconstruction. Because of limited data comparing complication rates on patients undergoing prepectoral breast reconstruction, this study compared 30-day postoperative complications by plane of prosthetic placement. METHODS: A retrospective review was conducted on all consecutive patients undergoing nipple-sparing mastectomy with implant-based reconstruction with either prepectoral or subpectoral placement from 2014 to 2018. The primary outcome was a composite, acute 30-day postoperative complication, including nipple-areola complex necrosis, mastectomy flap necrosis, wound dehiscence, infection, hematoma, and seroma. Secondary outcomes included nipple loss and rates of unintended reoperations. Univariate and mixed effects multivariate logistic regression were used to compare outcomes. RESULTS: A total of 228 patients and 405 breasts were included in the final cohort, with 202 in the subpectoral cohort and 203 in the prepectoral cohort. The overall complication rate was 7.65 percent, with no significant difference between subpectoral and prepectoral cohorts (9.41 percent versus 5.91 percent, respectively; p = 0.148). Prepectoral reconstruction was associated with significantly reduced ischemic complications, including nipple loss because of necrosis (2.97 percent versus 0.49 percent, respectively; p = 0.015) and mastectomy flap necrosis (5.45 percent versus 0 percent; p = 0.003). There were no significant differences in rates of infection, hematoma, seroma, or implant loss/exchange. CONCLUSIONS: Prepectoral reconstruction is associated with similar overall 30-day postoperative complications and reoperations compared to traditional subpectoral implants. However, prepectoral reconstruction was associated with significantly decreased ischemic complications, including mastectomy flap necrosis and nipple-areola complex loss because of necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Erratum: Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.].

Circulating endothelial progenitor cells correlate to stage in patients with invasive breast cancer.

Tumor growth and metastasis is dependent on the formation and assembly of new blood vessels, a process known as neo-angiogenesis. Both pre-existing and circulating vascular cells have been shown to contribute to the assembly of tumor neo-vessels in specific tumors. Mobilization of endothelial progenitor cells (EPCs) from the bone marrow constitutes a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be increased in certain malignant states. However, the role of circulating EPCs in breast cancer is largely unknown. We recruited twenty-five patients with biopsy-proven invasive breast cancer at Weill Cornell Breast Center to participate in a pilot study investigating the correlation of circulating EPCs to extent of disease and initiation of chemotherapy. For each patient, a baseline sample was drawn before systemic treatment, and for seventeen of those patients, a second sample was taken after the first round of chemotherapy. Levels of peripheral blood EPCs, as defined by co-expression of CD133 and VEGFR2, were quantified by flow cytometry. Breast cancer patients with stage III & IV disease had statistically higher levels of circulating EPCs than did patients with stage I & II disease (median = 165,000 EPCs/5 x 10(6)MNCs vs. median = 6,920 EPCs/5 x 10(6)MNCs, respectively, P < 0.0001). In addition, in late-stage patients, levels of EPCs demonstrated a statistically significant drop after initiation of chemotherapy (median = 162,500 EPCs/5 x 10(6)MNCs [pre] vs. median = 117,500 EPCs/5 x 10(6)MNCs [post], P = 0.01). These results suggest that circulating EPCs may serve as a potential tumor biomarker in breast cancer and that EPCs may represent a plausible target for future therapeutic intervention.

Breast Cancer following Augmentation Mammaplasty: A Case-Control Study.

BACKGROUND: The purpose of this study was to determine whether augmentation mammaplasty, implant type, and implant location affect breast cancer detection, stage, and treatment. METHODS: An institutional case-control study was performed of patients with prior breast augmentation undergoing breast cancer treatment from 2000 to 2013. Controls were propensity matched and randomized, and data were retrospectively reviewed. RESULTS: Forty-eight cases and 302 controls were analyzed. Palpable lesions were detected at a smaller size in augmentation patients (1.6 cm versus 2.3 cm; p < 0.001). Fewer lesions in augmented patients were detected by screening mammography (77.8 percent of cases versus 90.7 percent of controls; p = 0.010). Patients with implants were more likely to undergo an excisional biopsy for diagnosis (20.5 percent versus 4.4 percent; p < 0.001), rather than image-guided core needle biopsy (77.3 percent versus 95.3 percent; p < 0.001). Earlier staging in augmented patients approached but did not reach statistical significance (p = 0.073). Augmented patients had higher mastectomy rates (74.5 percent versus 57.0 percent) and lower rates of breast-conservation therapy (25.5 percent versus 43 percent; p = 0.023). Neither implant fill type nor anatomic location affected method of diagnosis, stage, or treatment. CONCLUSIONS: Palpable detection of breast cancer is more likely at a smaller size in augmented patients, yet it is less likely on screening mammography than in controls. Augmentation breast cancer patients have a comparable disease stage and are more likely to undergo mastectomy rather than lumpectomy. Both silicone and saline implants, whether placed submuscularly or subglandularly, have comparable effects on breast imaging, biopsy modality, and surgical intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

A Prospective Analysis of Quality of Life and Toxicity Outcomes in Treating Early Breast Cancer With Breast Conservation Therapy and Intraoperative Radiation Therapy.

Introduction: Intraoperative radiation therapy (IORT) is a minimally invasive radiation option for select patients with early stage breast cancer. This prospective, single institution, pilot study summarizes patient-reported quality of life (QoL) outcomes and clinician-reported toxicity following IORT following breast conservation therapy. Methods: Forty-nine patients were enrolled in a prospective study from 2013 until 2015 to assess QoL and toxicity following breast conservation therapy and IORT. Nine patients did not meet criteria for IORT alone on final pathology and required whole breast irradiation afterwards. These patients were evaluated separately. Validated QoL questionnaires were provided to patients at 1-week, 1-month, and subsequent 6-month intervals for 2 years. Radiation-related toxicity symptoms were evaluated by clinicians at the same time intervals. Likert scale responses were converted to continuous variables to depict patient-reported and clinician-reported outcomes. Results: Outcomes were analyzed as weighted averages of the Likert scale for each symptom. Responses for negative QoL symptoms ranged largely from 0 (none) to 2 (moderate). Responses for positive QoL symptoms ranged largely from 3 (quite a bit) to 4 (very much). Seventy-five percent of patients developed a toxicity; however, 99% of the toxicities were grades 1 and 2. All toxicities demonstrated a downward trend over time, with the exception of breast fibrosis and nodularity, which increased over time. There were no local recurrences upon 2-year follow up. Conclusion: Early stage breast cancer treated with IORT yields favorable QoL outcomes and minimal toxicity profiles with adequate short-term local control.

Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice.