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Background: Inter-rater reliability between breast surgical oncologists and reconstructive surgeons using cosmesis scales, and the correlation between their observations and patients' own subjective assessments, is poorly understood., Methods: Patients undergoing BCS in a prospective trial rated their cosmetic outcome on a Likert scale (poor/fair/good/excellent) at the postoperative and 1-year time points; photographs were also taken. Three breast surgical oncologists (not involved in these cases) and two reconstructive surgeons were asked to independently rate cosmesis using the Harvard/NSABP/RTOG scale., Results: Overall, 55 and 17 patients had photographs and Likert self-evaluations at the postoperative and 1-year time points, respectively. There was poor agreement between surgeon and patient ratings postoperatively [kappas - 0.042 (p = 0.659), 0.069 (p = 0.226), and 0.076 (p = 0.090) for the breast surgical oncologists; and 0.018 (p = 0.689) and 0.112 (p = 0.145) for the reconstructive surgeons], and poor interobserver agreement between surgeons of the same specialty (kappa - 0.087, 95% confidence interval [CI] - 0.091 to - 0.082, p = 0.223 for breast surgical oncologists; and kappa - 0.150, 95% CI - 0.157 to - 0.144, p = 0.150, for reconstructive surgeons). At 1 year, the interobserver agreement between breast surgical oncologists was better (kappa 0.507, 95% CI 0.501-0.512, p < 0.001); however, there was still poor correlation between the reconstructive surgeons (kappa - 0.040, 95% CI - 0.049 to - 0.031, p = 0.772). Agreement between surgeon and patient ratings remained poor at this time point [kappas - 0.115 (p = 0.477), 0.177 (p = 0.245), and 0.101 (p = 0.475) for breast surgical oncologists; and 0.335 (p = 0.037) and -0.118 (p = 0.221) for reconstructive surgeons]., Conclusion: Despite gradation scales for measuring cosmesis after BCS, high levels of agreement between surgeons is lacking and these do not always reflect patients' subjective assessments., (© 2021. Society of Surgical Oncology.)

Introduction: Invasive apocrine carcinoma is a rare breast cancer that is frequently triple negative. Little is known about the characteristics of its molecular subtypes. We compared the incidence, demographics, and clinicopathologic features of this cancer with non-apocrine carcinomas stratified by molecular subtype., Methods: Women with invasive apocrine cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathologic and demographic features were compared with non-apocrine carcinomas, both overall using data from 2004 to 2017 and stratified by molecular subtypes using data from 2010 to 2017. The life table method was used to determine the 7-year breast cancer-specific survival., Results: Compared with non-apocrine cancers, apocrine cancers presented at a younger age, with larger, higher-grade tumors that were much more likely to be triple negative (50% vs. 11%) or human epidermal growth factor receptor 2 (HER2)-positive (28% vs. 15%) and less likely to be luminal (22% vs. 74%); however, the 7-year survival was the same at 85%. The characteristics varied dramatically by molecular type. Compared with non-apocrine triple-negative, apocrine triple-negative patients were less likely to be African American and were much older, with smaller, lower-grade tumors and much better survival (86% vs. 74%). In contrast, compared with luminal non-apocrine, apocrine luminal patients had larger, higher-grade tumors and worse survival (79% vs. 89%)., Conclusions: Invasive apocrine carcinomas have more aggressive features than non-apocrine carcinomas but the breast cancer-specific survival is the same. Half of these apocrine tumors are triple negative but these have more favorable features and much better survival than non-apocrine triple-negative cancers., (© 2021. Society of Surgical Oncology.)

Background: Angiosarcoma of the breast is rare and aggressive. It can occur as a de novo tumor or secondary to breast cancer treatment. The purpose of this study is to analyze differences between patients with primary and secondary angiosarcoma of the breast and investigate potential risk factors for its development., Patients and Methods: The Surveillance, Epidemiology, and End Results program of the National Cancer Institute database was queried to identify patients with angiosarcoma of the breast, trunk, shoulder, and upper arm. The population-based incidence was analyzed. Primary and secondary angiosarcoma cases were identified and compared. Breast cancer characteristics of secondary angiosarcoma patients were compared with all breast cancer patients in the database who did not develop angiosarcoma., Results: Overall, 904 patients were included, and 65.4% were secondary angiosarcomas. These patients had worse survival, were older, more likely to be White, more likely to have regionally advanced disease, and had angiosarcoma tumors of higher pathologic grade. Independent factors associated with development of secondary angiosarcoma among breast cancer patients included White race, older age, invasive tumor, lymph node removal, lumpectomy, radiation treatment, and left-sided tumor. Although the mean time to develop angiosarcoma after breast cancer diagnosis was 8.2 years, the risk continues to increase up to 30 years after breast cancer treatment., Conclusion: Angiosarcoma is rare but increasing in incidence. Secondary angiosarcomas are more common and exhibit more aggressive behavior. Several factors for angiosarcoma after breast cancer treatment could be identified, which may help us counsel and identify patients at risk., (© 2021. Society of Surgical Oncology.)

Introduction: Timing of autologous reconstruction relative to postmastectomy radiation therapy (PMRT) is debated. Benefits of immediate reconstruction must be weighed against a possibly heightened risk of complications from flap irradiation. We reviewed flap outcomes after single operation plus PMRT in a large institutional cohort., Methods: Medical records were reviewed for women who underwent simultaneous mastectomy-autologous reconstruction with PMRT from 2007 to 2016. Primary endpoints were rates and types of radiation-related flap complications and reoperations, whose predictors were assessed by multivariable analysis. A p value < 0.10 was deemed significant to avoid type II error. Non-parametric logistic regression generated a model of PMRT timing associated with probabilities of complications and reoperations., Results: One-hundred and thirty women underwent 208 mastectomy reconstruction operations, with a median follow up of 35.1 months (interquartile range 23.6-56.5). Forty-seven (36.2%) women experienced radiation-related complications, commonly fat necrosis (44.1%) and chest wall asymmetry (28.8%). Complications were higher among women who received PMRT < 3 months after surgery (46.8% for < 3 months vs. 29.3% for ≥ 3 months; p = 0.06), most of whom received neoadjuvant chemotherapy, and among women treated with internal mammary nodal (IMN) radiation (65.2% vs. 26.4%; p < 0.01); IMN radiation remained strongly associated in multivariable analysis (odds ratio [OR] 5.24; p < 0.01). Thirty-two (24.6%) women underwent 70 reoperations, commonly fat grafting (51.9%) and fat necrosis excision (17.1%). Reoperations were higher among women who received PMRT < 3 months after surgery (48.9 for < 3 months vs. 36.6 for ≥ 3 months; p = 0.19), which was significantly associated in multivariable analysis (OR 0.42; p = 0.08 for ≥ 3 months). The probabilities of complications and reoperations were lowest when PMRT was administered ≥ 3 months after surgery., Conclusions: Among a large institutional cohort, immediate autologous reconstruction was associated with similar rates of adverse flap outcomes as historically reported alternatively sequenced protocols. IMN radiation increased risk, while PMRT ≥ 3 months after surgery decreased risk. Additional studies are needed to elaborate the impact of IMN radiation and early PMRT in immediate versus delayed autologous reconstruction.

Background: Some suggest that lymph node (LN) evaluation not be performed routinely in women aged ≥70 years with clinically (c) LN-negative (-), hormone receptor (HR)-positive (+) breast cancer. We sought to determine the association of omission of LN evaluation on survival., Methods: Patients who met the above criteria and were diagnosed from 2004 to 2012 were identified in the NCDB and SEER databases. Overall survival (OS) and breast cancer-specific survival (BCSS) were determined., Results: Using the NCDB, we identified 157,584 cLN- HR+ patients aged ≥70 years in whom survival and LN evaluation data were available. A total of 126,638 patients (80.2%) had regional LN surgery. With a median follow-up of 41.6 months, there was a significant difference in OS between those who had LN evaluation and those who did not (median OS: 100.5 vs. 70.9 months, respectively, p < 0.001). After adjusting for patient age, race, insurance, income, comorbidities, tumor characteristics and treatment, patients who had undergone LN evaluation still had a lower hazard rate for death than those who had not (hazard ratio = 0.633; 95% confidence interval [CI] 0.613-0.654, p < 0.001). We then did a parallel analysis using SEER data that showed LN evaluation was associated with a lower hazard rate for both BCSS (hazard ratio = 0.452; 95% CI 0.427-0.479, p < 0.001) and non-BCSS (hazard ratio = 0.465; 95% CI 0.447-0.482, p < 0.001)., Conclusions: Roughly 20% of patients older than aged 70 years with cLN-, HR+ breast cancer did not have LN evaluation. Those who did had better OS controlling for sociodemographic, pathologic, and treatment variables; however, this may be due to patient selection.

Background: Whether rates of breast-conservation surgery (BCS) vary based on race and ethnicity has not been clearly elucidated on a national leve., Methods: The National Cancer Data Base (NCDB) was used to identify women who underwent surgery for invasive breast cancer during 2010 and 2011. The effect of race and ethnicity on BCS rates was determined, independent of patient demographics, tumor-related variables, and geographic region., Results: There were 299,827 patients with known race and ethnicity who underwent definitive breast surgery. BCS rates by race were as follows: 135,065/241,236 (56.0 %) for whites, 17,819/33,301 (53.5 %) for blacks, 4,722/9,508 (49.7 %) for Asian/Pacific Islanders, and 7,919/15,782 (50.2 %) for Hispanics (p < 0.001). Mean tumor size differed among the racial groups: 2.07 cm in whites, 2.54 cm in blacks, 2.23 cm in Asians, and 2.48 cm in Hispanics (p < 0.001). When stratified by tumor size, BCS was most common in blacks and least common in Asians for all tumors >2 cm (p < 0.001). On multivariable analysis adjusted for age, tumor size, nodal status, grade, molecular type, geographic area, urban/rural residence, insurance status, and census-derived median income and education for the patient's zip code, the odds ratio for BCS for blacks compared to whites was 1.23 (95 % confidence interval [CI] 1.20-1.27, p < 0.001), for Asians was 0.84 (95 % CI 0.80-0.88, p < 0.001), and for Hispanics was 1.00 (95 % CI 0.96-1.05, p = 0.885)., Conclusions: When adjusted for patient demographics, tumor-related variables, and geographic area, BCS rates are higher in blacks and lower in Asians compared to whites.

Background: Multifocality and multicentricity are increasingly recognized in breast cancer. However, little is known about the characteristics and biology of these cancers and the clinical implications are controversial., Methods: A retrospective, institutional database was used to compare characteristics of multifocal (MF) and multicentric (MC) breast cancers with unifocal (UF) cancers to study concordance of histology and receptor status among primary and secondary foci and to evaluate predictors of lymph node positivity using multivariate logistic regression., Results: Of 1495 invasive cancers, 1231 (82.3 %) were UF, 169 (11.3 %) were MF, and 95 (6.4 %) were MC cancers. When MF and MC cancers were compared with UF cancers, MC but not MF cancers were associated with young age at diagnosis, larger tumor size, lymphovascular invasion, and node positivity. MF but not MC tumors were more likely to be ER/PR+Her2+ tumors and less likely to be triple-negative cancers compared with UF tumors. MF tumors were more likely to be infiltrating ductal carcinomas with an extensive intraductal component, and MC tumors were more likely to be infiltrating lobular carcinomas. Concordance of histology and receptor status between primary and secondary foci was high and was similar for both MF and MC cancers. Multicentricity remained an independent predictor of lymph node positivity on multivariate analysis., Conclusion: MF and MC tumors seem to be biologically different diseases. MC is clinicopathologically more aggressive than MF disease and is more frequently associated with younger age and larger tumor size and also is an independent predictor of node positivity.

Background: Recent trials have suggested that axillary node dissection may not be warranted in some breast cancer patients with one to two positive nodes. Given that lymph node ratio (LNR; number of positive lymph nodes divided by the total examined) has been shown to be a significant prognostic factor, we sought to determine whether the number of nodes removed in this low risk population predicted survival., Methods: The National Cancer Database is a comprehensive clinical surveillance resource capturing 70% of newly diagnosed malignancies in the United States; 309,216 breast cancer patients diagnosed between 1998 and 2005, with tumors ≤5 cm and one to two positive nodes, formed the cohort of interest., Results: Median age at diagnosis was 57 (range 18-90) years. Median tumor size was 2 (range 0.1-5) cm; 215,382 patients (69.7%) had one positive node, and 93,834 (30.3%) had two. The median number of lymph nodes examined was 11 (range 1-84). Patients were categorized into low (≤0.2), medium (0.21-0.65), or high (>0.65) LNR groups, with 228,822 (74%), 55,797 (18%), and 24,597 (8%) patients in each of these categories, respectively. Median follow-up was 54.1 months. Median overall survival (OS) for low, intermediate, and high LNR was 66.1, 61.1, and 56.5 months, respectively (p < 0.001). In a Cox model controlling for clinicopathologic and therapy covariates, LNR category remained a significant predictor of OS (p < 0.001)., Conclusions: LNR is an independent predictor of OS in a low-risk population with one to two positive nodes and tumors ≤5 cm. Therefore, the number of lymph nodes excised may influence prognostic stratification.

Background: The identification of distinct molecular subtypes has changed breast cancer management. The correlation between mammographic appearance and molecular subtype for invasive breast cancer has not been extensively studied., Methods: A retrospective review of our prospectively collected database was performed to evaluate the mammographic appearance and molecular subtypes of all cases of invasive breast cancers diagnosed between 2003 and 2010., Results: There were 985 cases of invasive breast cancer with complete data on receptor status and mammographic appearance. The most common mammographic finding was a mass (61 %), and the most common molecular subtype was ER/PR positive, HER2 negative (71 %). On univariate analysis, race, stage, and histology were all significantly associated with molecular subtype. On multivariate analysis, the luminal molecular type was associated with architectural distortion [odds ratio (OR) 4.3, 95 % CI 1.3-14.1]; HER2 positive cancers, either with or without ER/PR expression, were more likely to be associated with mammographic calcifications (OR 2.8 and 3.1, respectively; 95 % CI 1.7-4.8 and 1.7-5.5); and triple negative cancers were most likely to be associated with a mammographic mass (OR 2.5; 95 % CI 1.4-4.4)., Conclusions: We observed several characteristic associations between molecular subtype and mammographic appearance. Improved understanding of these associations may help guide clinical decision making and provide information about underlying tumor biology.

Introduction: Although controversial, the use of breast magnetic resonance imaging (MRI) is widespread. We sought to determine factors that influenced its use in a population-based sample., Methods: The National Health Interview Survey is conducted annually by the Centers for Disease Control and is designed to be representative of the American population. Data from 2010 were queried for the use of breast MRI and associated sociodemographic and risk characteristics., Results: Of the 11,222 women aged ≥30 years who were surveyed, 4.7 % reported ever having a breast MRI. Nearly a quarter were done as part of a "routine exam" and <5 % were done for "family history" or for "high risk." Factors correlating with MRI use on univariate analysis included age, race, personal and/or family history of breast cancer, history of benign breast biopsy, perceived risk, and insurance. On multivariate analysis, African-American race (p = 0.001), personal history (p < 0.001), history of benign biopsy (p < 0.001), and high perceived risk (p < 0.001) were significantly associated with increased MRI use. In a cohort without a personal history of breast cancer, race, history of benign biopsy, and perceived risk were independent correlates of breast MRI, whereas family history, age, and insurance were no longer significant., Conclusions: Personal history is the strongest factor associated with breast MRI use. However, whereas race, history of benign biopsy, and perceived risk were independently associated with MRI use, family history was not. These findings call into question whether current practice patterns follow evidence-based guidelines.

Introduction: It is accepted that preoperative chemotherapy can result in increased breast preservation for breast cancers greater than 4 cm. The benefits of preoperative chemotherapy are less clear, however, for patients who present with smaller tumors and are already candidates for breast-preserving surgery. The goal of this study is to assess the effect of preoperative chemotherapy on breast cancers between 2 and 4 cm diameter., Methods: A retrospective chart review was conducted of patients diagnosed with new breast cancer at the Yale-New Haven Breast Center for the years 2002-2007. Patients were included in the study if their breast cancer was between 2 and 4 cm and their initial surgical treatment had been completed. Patients with distant metastases were excluded., Results: There were 156 new cancers that met study requirements. Forty-seven patients underwent preoperative chemotherapy, and 109 patients had their surgery first, usually followed by chemotherapy. Initial surgery was lumpectomy for 31 out of 47 patients (66%) in the preoperative chemotherapy group compared with 62 out of 109 patients (57%) in the surgery group. For patients with lumpectomies, 2 out of 31 patients (6%) in the preoperative group had positive margins and required re-excision compared with 20 out of 62 patients (37%) in the surgery-first group (P<0.01)., Conclusions: We conclude that, for tumors between 2 and 4 cm, preoperative chemotherapy is associated with a significantly decreased rate of re-excision following lumpectomy. This not only results in fewer mastectomies, but also avoids the morbidity and inferior cosmetic results associated with a re-excision lumpectomy.