Insulin resistance and racial disparities in breast cancer prognosis: a multi-center cohort study.

The survival for breast cancer (BC) is improving but remains lower in Black women than White women. A number of factors potentially drive the racial differences in BC outcomes. The aim of our study was to determine if insulin resistance (defined as homeostatic model assessment for insulin resistance (HOMA-IR)), mediated part of the relationship between race and BC prognosis (defined by the improved Nottingham prognostic index (iNPI)). We performed a cross-sectional study, recruiting self-identified Black and White women with newly diagnosed primary invasive BC from 10 US hospitals between March 2013 and February 2020. Survey, anthropometric, laboratory, and tumor pathology data were gathered, and we compared the results between Black and White women. We calculated HOMA-IR as well as iNPI scores and examined the associations between HOMA-IR and iNPI. After exclusions, the final cohort was 1206: 911 (76%) White and 295 (24%) Black women. Metabolic syndrome and insulin resistance were more common in Black than White women. Black women had less lobular BC, three times more triple-negative BC, and BCs with higher stage and iNPI scores than White women (P < 0.001 for all comparisons). Fewer Black women had BC genetic testing performed. HOMA-IR mediated part of the association between race and iNPI, particularly in BCs that carried a good prognosis and were hormone receptor (HR)-positive. Higher HOMA-IR scores were associated with progesterone receptor-negative BC in White women but not Black women. Overall, our results suggest that HOMA-IR contributes to the racial disparities in BC outcomes, particularly for women with HR-positive BCs.

Mastectomy or Margin Re-excision? A Nomogram for Close/Positive Margins After Lumpectomy for DCIS.

BACKGROUND: Anatomic extent of ductal carcinoma in situ (DCIS) may be uncertain in spite of clinical, pathologic, and imaging data. Consequently close/positive margins are common with lumpectomy for DCIS and often lead to a challenge in deciding whether to perform a re-excision or mastectomy. PATIENTS AND METHODS: From a single health system, we identified cases of lumpectomy for DCIS with close/positive margins who underwent re-excision for the purpose of constructing a nomogram. In total, 289 patients were available for analysis. The patients were randomly divided into two sets allocating 70% to the modeling and 30% to the validation set. A multivariable logistic regression model was used to estimate the probability of overall positive margin status using multiple clinicopathologic predictors. Nomogram validation included internal tenfold cross-validation, internal bootstrap validation, and external validation for which a concordance index was calculated to assess the external validity. RESULTS: Significant predictors of persistent positive margins from regression modeling included necrosis at diagnosis (non-comedo or comedo); DCIS not associated with calcifications on core biopsy; high-grade DCIS; progesterone receptor positivity; and number of positive margins at initial surgery. When subjected to internal validation, the nomogram achieved an uncorrected concordance index of 0.7332, a tenfold cross-validation concordance index of 0.6795, and a bootstrap-corrected concordance index of 0.6881. External validation yielded an estimated concordance index of 0.7095. CONCLUSION: Using clinical and pathologic variables from initial diagnosis and surgery for DCIS, this nomogram predicts persistent positive margins with margin re-excision, and may be a valuable tool in surgical decision-making.

Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial.

BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method. RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation. CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.

Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score.

BACKGROUND: Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX™ (ODX) recurrence scores has been observed to explain this health disparity. Black women are also disproportionately affected by insulin resistance. We evaluated whether insulin resistance is associated with a higher ODX recurrence score and whether there is a difference between White and Black women to explain disparate clinical outcomes. METHODS: A subgroup analysis of patients in a multi-institutional cross-sectional study evaluating differences in insulin resistance between White and Black women was performed. Women diagnosed with a new hormone receptor-positive, HER2/neu-negative breast cancer with an ODX recurrence score were identified. Fasting blood glucose and insulin measurements were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) score, a method for assessing insulin resistance, and compared against ODX scores. RESULTS: Overall, 412 women (358 White women, 54 Black women) were identified. Compared with White women, Black women had a higher body mass index (30 vs. 26 kg/m2, p < 0.0001), higher HOMA-IR score (2.4 vs. 1.4, p = 0.004), and more high-grade tumors (30% vs. 16%, p = 0.01). There was a direct positive association with an increasing ODX score and HOMA-IR (p = 0.014). On subset analysis, this relationship was seen in White women (p = 0.005), but not in Black women (p = 0.55). CONCLUSION: In women with newly diagnosed breast cancer, increasing insulin resistance is associated with a higher recurrence score; however, this association was not present in Black women. This lack of association may be due to the small number of Black women in the cohort, or possibly a reflection of a different biological disease process of the patient's tumor.

Insulin resistance contributes to racial disparities in breast cancer prognosis in US women.

BACKGROUND: Racial disparities in breast cancer survival between Black and White women persist across all stages of breast cancer. The metabolic syndrome (MetS) of insulin resistance disproportionately affects more Black than White women. It has not been discerned if insulin resistance mediates the link between race and poor prognosis in breast cancer. We aimed to determine whether insulin resistance mediates in part the association between race and breast cancer prognosis, and if insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R) expression differs between tumors from Black and White women. METHODS: We conducted a cross-sectional, multi-center study across ten hospitals. Self-identified Black women and White women with newly diagnosed invasive breast cancer were recruited. The primary outcome was to determine if insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR), mediated the effect of race on prognosis using the multivariate linear mediation model. Demographic data, anthropometric measurements, and fasting blood were collected. Poor prognosis was defined as a Nottingham Prognostic Index (NPI) > 4.4. Breast cancer pathology specimens were evaluated for IR and IGF-1R expression by immunohistochemistry (IHC). RESULTS: Five hundred fifteen women were recruited (83% White, 17% Black). The MetS was more prevalent in Black women than in White women (40% vs 20%, p < 0.0001). HOMA-IR was higher in Black women than in White women (1.9 ± 1.2 vs 1.3 ± 1.4, p = 0.0005). Poor breast cancer prognosis was more prevalent in Black women than in White women (28% vs 15%. p = 0.004). HOMA-IR was positively associated with NPI score (r = 0.1, p = 0.02). The mediation model, adjusted for age, revealed that HOMA-IR significantly mediated the association between Black race and poor prognosis (ß = 0.04, 95% CI 0.005-0.009, p = 0.002). IR expression was higher in tumors from Black women than in those from White women (79% vs 52%, p = 0.004), and greater IR/IGF-1R ratio was also associated with higher NPI score (IR/IGF-1R >  1: 4.2 ± 0.8 vs IR/IGF-1R = 1: 3.9 ± 0.8 vs IR/IGF-1R < 1: 3.5 ± 1.0, p < 0.0001). CONCLUSIONS: In this multi-center, cross-sectional study of US women with newly diagnosed invasive breast cancer, insulin resistance is one factor mediating part of the association between race and poor prognosis in breast cancer.

Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. the COVID-19 pandemic breast cancer consortium.

The COVID-19 pandemic presents clinicians a unique set of challenges in managing breast cancer (BC) patients. As hospital resources and staff become more limited during the COVID-19 pandemic, it becomes critically important to define which BC patients require more urgent care and which patients can wait for treatment until the pandemic is over. In this Special Communication, we use expert opinion of representatives from multiple cancer care organizations to categorize BC patients into priority levels (A, B, C) for urgency of care across all specialties. Additionally, we provide treatment recommendations for each of these patient scenarios. Priority A patients have conditions that are immediately life threatening or symptomatic requiring urgent treatment. Priority B patients have conditions that do not require immediate treatment but should start treatment before the pandemic is over. Priority C patients have conditions that can be safely deferred until the pandemic is over. The implementation of these recommendations for patient triage, which are based on the highest level available evidence, must be adapted to current availability of hospital resources and severity of the COVID-19 pandemic in each region of the country. Additionally, the risk of disease progression and worse outcomes for patients need to be weighed against the risk of patient and staff exposure to SARS CoV-2 (virus associated with the COVID-19 pandemic). Physicians should use these recommendations to prioritize care for their BC patients and adapt treatment recommendations to the local context at their hospital.

The effect of modifiable risk factors on breast cancer aggressiveness among black and white women.

INTRODUCTION: Although breast cancer incidence is higher among white women, black women are more likely to have aggressive tumors with less favorable histology, and to have a worse prognosis. Obesity and alcohol consumption have been identified as two modifiable risk factors for breast cancer, while physical activity may offer protection. Little however is known about the association of these factors with race on the severity of breast cancer. METHODS: Data collected as part of a large prospective study looking at insulin resistance and race among women with breast cancer was queried for patient characteristics, lifestyle factors and tumor characteristics. The association with Nottingham Prognostic Index (NPI) was assessed with different models using univariate and multivariate linear regression. RESULTS: Among 746 women in our cohort, 82% (n = 615) were white and 18% (n = 131) were black, mean age 58 years. Black patients were more likely to have high BMI (31.0 vs. 26.7, p < 0.0001), comorbidities (69% vs 55%, p = 0.01), self-reported poor diet (70% vs 42%, p < 0.001), be sedentary (56% vs 46%, p = 0.03) and were less likely to consume alcohol (8% vs 32%, p < 0.0001) compared to white patients. Overall, 137 (18%) of the patients had poorer prognosis (NPI > 4.4), which was significantly associated with younger age (55.6 vs 58.5 years, p = 0.02), black race (27% vs 15%, p = 0.001), triple negative cancer (15% vs 6%, p = 0.003), and poor diet (54% vs 45%, p = 0.046) compared to patients with better prognosis (NPI ≤ 4.4). On multivariate analysis, (model R2 = 0.12; p < 0.001), age (ß = -0.011 per year, p = 0.002), healthy diet (ß = -0.195, p = 0.02), and exercise (ß = -0.004, p = 0.02) were associated with better prognosis, while black race (ß = 0.247, p = 0.02) and triple negative cancer (ß = 0.908, p < 0.0001) were associated with poor prognosis. Neither alcohol use nor BMI was significantly associated with NPI. CONCLUSION: Among modifiable risk factors, diet and exercise are associated with NPI. Unmodifiable factors including race and biologic subtype remain the most important determinants of prognosis.

Genomic comparison of paired primary breast carcinomas and lymph node macrometastases using the Oncotype DX Breast Recurrence Score® test.

PURPOSE: Adjuvant therapy decisions may in part be based on results of Oncotype DX Breast Recurrence Score® (RS) testing of primary tumors. When necessary, lymph node metastases may be considered as a surrogate. Here we evaluate the concordance in gene expression between primary breast cancers and synchronous lymph node metastases, based on results from quantitative RT-PCR-based RS testing between matched primary tumors and synchronous nodal metastases. METHODS: This retrospective, exploratory study included patients (≥ 18 years old) treated at our center (2005-2009) who had ER+ , HER2-negative invasive breast cancer and synchronous nodal metastases with available tumor blocks from both sites. Paired tissue blocks underwent RS testing, and RS and single-gene results for ER, PR, and HER2 were explored between paired samples. RESULTS: A wide distribution of RS results in tumors and in synchronous nodal metastases were modestly correlated between 84 paired samples analyzed (Pearson correlation 0.69 [95% CI 0.55-0.78]). Overall concordance in RS group classification between samples was 63%. ER, PR, and HER2 by RT-PCR between the primary tumor and lymph node were also modestly correlated (Pearson correlation [95% CI] 0.64 [0.50-0.75], 0.64 [0.49-0.75], and 0.51 [0.33-0.65], respectively). Categorical concordance (positive or negative) was 100% for ER, 77% for PR, and 100% for HER2. CONCLUSIONS: There is modest correlation in continuous gene expression, as measured by the RS and single-gene results for ER, PR, and HER2 between paired primary tumors and synchronous nodal metastases. RS testing for ER+ breast cancer should continue to be based on analysis of primary tumors.

Consensus Guidelines on Genetic` Testing for Hereditary Breast Cancer from the American Society of Breast Surgeons.

BACKGROUND: The purpose of this consensus guideline is to outline recommendations for genetic testing that medical professionals can use to assess hereditary risk for breast cancer. METHODS: Literature review included large datasets, basic and clinical science publications, and recent updated national guidelines. Genetic testing to assess hereditary risk of cancer is a complex, broad, and dynamic area of medical research. The dominant focus of this guideline is limited in scope to breast cancer. RESULTS: There is a lack of consensus among experts regarding which genes among many should be tested in different clinical scenarios. There is also variation in the degree of consensus regarding the understanding of risk and appropriate clinical management of mutations in many genes. CONCLUSIONS: Genetic testing should be made available to all patients with a personal history of breast cancer. Recent data are reviewed that support genetic testing being offered to each patient with breast cancer (newly diagnosed or with a personal history). If genetic testing is performed, such testing should include BRCA1/BRCA2 and PALB2, with other genes as appropriate for the clinical scenario and family history. For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations. Patients who had genetic testing previously may benefit from updated testing. Genetic testing should be made available to patients without a history of breast cancer who meet National Comprehensive Cancer Network guidelines. Finally, variants of uncertain significance are not clinically actionable and these patients should be managed based on their individual risk factors.

The 2018 Compensation Survey of the American Society of Breast Surgeons.

BACKGROUND: There is limited compensation data for breast surgery benchmarking. In 2018, the American Society of Breast Surgeons conducted its second membership survey to obtain updated compensation data as well as information on practice type and setting. METHODS: In October 2018, a survey was emailed to 2676 active members. Detailed information on compensation was collected, as well as data on gender, training, years in and type of practice, percent devoted to breast surgery, workload, and location. Descriptive statistics and multivariate analyses were performed to analyze the impact of various factors on compensation. RESULTS: The response rate was 38.2% (n = 1022, of which 73% were female). Among the respondents, 61% practiced breast surgery exclusively and 54% were fellowship trained. The majority of fellowship-trained surgeons within 5 years of completion of training (n = 126) were female (91%). Overall, mean annual compensation was $370,555. On univariate analysis, gender, years of practice, practice type, academic position, ownership, percent breast practice, and clinical productivity were associated with compensation, whereas fellowship training, region, and practice setting were not. On multivariate analysis, higher compensation was significantly associated with male gender, years in practice, number of cancers treated per year, and wRVUs. Compensation was lower among surgeons who practiced 100% breast compared with those who did a combination of breast and other surgery. CONCLUSIONS: Differences in compensation among breast surgeons were identified by practice type, academic position, ownership, years of practice, percent breast practice, workload, and gender. Overall, mean annual compensation increased by $40,000 since 2014.

A novel, adaptable, radiographically opaque, multi-plane continuous filament marker for optimizing tissue identification, radiation planning, and radiographic follow-up.

BACKGROUND: In breast cancer treatment, marking the tumor bed is an important aspect of the surgical component of therapy. Clear delineation of the tumor bed allows radiation oncologists a defined target for planning and delivering postoperative radiation therapy (XRT). Tumor bed marking also allows radiographic follow-up of the tumor bed on subsequent breast imaging. The aim of this assessment is to evaluate the ease and feasibility of utilizing a tumor bed filament marker (VeraFormÒ, Videra Surgical inc., USA) as a marker in post-operative benign surgical sites and malignant breast surgical tumor beds in breast cancer surgery. METHODS: The filament marker is a novel radiopaque surgical filament that in lieu of clips and other markers is implanted in the surgical tumor bed during breast surgery. Following development of the filament marker, the researchers used breast phantoms and radiographic images to develop a series of geometric patterns of placement options that optimize comprehensive multi-plane radiographic interpretation of the exact tumor bed or surgical margin. Three breast surgeons at 3 separate institutions then used this filament as a continuous multi-plane marker in 20 patients during breast conservation surgery. In these patients, the filament marker was thus used to mark the tumor bed (breast cancer surgery) or surgical site (benign breast disease) instead of the more traditional devices such as clips or other metallic open framework devices. We then assessed 2 important factors related to this device; (I) the ease, feasibility, and accuracy of in vivo placement with oncoplastic and non-oncoplastic breast conservation surgery techniques; (II) the radiographic footprint this device left on standard imaging protocols of post-operative mammogram (MMG), computed tomography (CT) scan, breast magnetic resonance imaging (MRI) examinations, and ultrasounds (USs) for both routine follow-up imaging and for standard radiation planning. RESULTS: There were no adverse events reported with the use of this device. The cases were then reviewed by a multidisciplinary team that included the original surgeon, a breast radiologist, and radiation oncologist. Their unanimous evaluation was that the filament marker clearly delineated all sides and planes of the tumor bed (cancer surgery) or surgical site (benign disease). Regardless of surgical technique utilized, this information provided precise 3D guidance for radiation planning and delivery as well as radiographic follow-up. The surgeons involved reported that delineating the bed with the filament marker was a quick and easy procedure and did not interfere with performing the planned surgical technique. Radiologists, surgeons, and radiation oncologists found that the filament marker was not only radiographically opaque on CT and MMG, but also caused no significant artifact on CT, MRI, US, or MMG. CONCLUSIONS: The continuous multi-plane filament marker is a new device that fulfills the heretofore unmet need for safe and improved tumor bed and tissue site marking. It is an easy to place, non-palpable continuous multi-plane radiographic opaque tissue marker that seems to better delineate the tumor bed, regardless of type of breast surgery performed, while providing a more accurate 3D image for radiation planning and radiographic follow-up on MMG MRI, CT and US.

Clinical Experience With Mammary Ductoscopy.

BACKGROUND: Most breast cancers begin in the ductal epithelium with normal cells and progress to atypia and finally to carcinoma. Mammary ductoscopy enables one to directly visualize and sample the ductal epithelium and, therefore, identify early changes cytologically. This article describes our initial experience with mammary ductoscopy at Beth Israel Medical Center. METHODS: A prospective review of all patients who underwent ductoscopy at Beth Israel Medical Center from November 2001 to February 2004 was performed. The indications for ductoscopy were a persistent nipple discharge, high-risk status, or intraoperative margin assessment in patients undergoing lumpectomy. RESULTS: Seventy-four patients underwent ductoscopic evaluation of 88 ducts. Of the 32 patients who underwent office ductoscopy, 15 were high risk, and 17 had spontaneous nipple discharge. Spontaneous nipple discharge was the indication for ductoscopy in 40 of 42 intraoperative procedures. The remaining two patients underwent ductoscopy for margin assessment during breast conservation, and final pathologic analysis revealed negative margins. Thirty-eight of the 40 patients who had spontaneous nipple discharge had abnormal findings during ductoscopy and therefore underwent ductoscopically guided duct excision. Carcinoma was the final diagnosis in 5 (8.8%) of the 57 patients who were scoped for nipple discharge. CONCLUSIONS: Mammary ductoscopy is a potentially useful tool in the evaluation of patients with spontaneous nipple discharge. This is a well-tolerated office procedure with minimal risks and complications. Mammary ductoscopy may have a role in the assessment of high-risk women. Further research is necessary to confirm these potential applications.

Factors influencing incidence and type of postmastectomy breast reconstruction in an urban multidisciplinary cancer center.

BACKGROUND: On January 1, 2011, New York State amended the Public Health Law to ensure that patients receive "information and access to breast reconstruction surgery." The purposes of this study were to investigate the early impact of this legislation on reconstruction rates and to evaluate the influence of patient variables versus physician variables on the incidence and type of breast reconstruction performed. METHODS: A retrospective study was conducted on all patients who underwent mastectomy between January 1, 2010, and December 31, 2011. Reconstruction rates were analyzed in relation to timing of legislation, breast surgeon variables, plastic surgeon faculty status, type of reconstruction, and patient variables. RESULTS: Two hundred fifty-eight patients met inclusion criteria. The overall reconstruction rate was 56.59 percent. There was no statistically significant increase in reconstruction rate after the 2011 legislation (OR, 0.45; p = 0.057). Patients whose breast surgeon was female were more likely to undergo reconstruction (OR, 5.17; p = 0.001). Patients who were Asian (OR, 0.22; p = 0.002), older than 60 years (OR, 0.09; p = 0.001), or had stage 3 and 4 cancer (OR, 0.04; p = 0.03) were less likely to undergo reconstruction. Patients reconstructed by a hospital-employed plastic surgeon were significantly more likely to undergo autologous versus implant reconstruction (OR, 6.85; p = 0.001) and to undergo microsurgical versus nonmicrosurgical autologous reconstruction (78.2 percent versus 0 percent; p = 0.001). CONCLUSIONS: Breast surgeon sex and plastic surgeon faculty status were the factors that most affected the rate and type of reconstruction, respectively. Legislation mandating the discussion of breast reconstruction options had no impact on reconstruction rate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Clinical significance of HER2-positive and triple-negative status in small (≤ 1 cm) node-negative breast cancer.

BACKGROUND: Data regarding the clinical significance of HER2(+) and TN status in patients with small node-negative tumors are limited and conflicting. It remains unclear who, among those with small lesions, might benefit from more aggressive adjuvant therapy. PATIENTS AND METHODS: We identified all node-negative breast cancer patients with tumor size ≤ 1 cm diagnosed between January 1, 1995 and December 31, 2008 using our institutional breast service database. Patients were classified according to their receptor status into 3 groups: (1) hormone receptor (HR)-positive (estrogen receptor [ER]- or progesterone receptor [PR]-positive, HER2(-)); (2) HER2(+) (immunohistochemistry 3(+) or fluorescence in situ hybridization amplification ≥ 2); and (3) TN (ER(-), PR(-), and HER2(-)). RFS was calculated using Kaplan-Meier methods. RESULTS: Among 656 patients with tumors ≤ 1 cm, 494 (75%) of the patients were HR(+), 107 (16%) were HER2(+), and 55 (9%) were TN. Median age was 59 years (range, 27-92 years). Median follow-up was 3.5 years. The 5-year RFS rates were 98.2%, 97.1%, and 83.5% in patients with HR(+), HER2(+), and TN tumors, respectively (P < .001). In multivariate analysis, TN status was associated with worse RFS (hazard ratio, 6.70; 95% confidence interval [CI], 3.02-14.86), and HER2(+) was not (hazard ratio, 1.64; 95% CI, 0.73-3.69). CONCLUSION: TN, but not HER2(+) status, was associated with worse RFS in patients with T1abN0 tumors, and adjuvant chemotherapy might be considered in patients with TN breast cancer.

A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies.

BACKGROUND: The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins. METHODS: This multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted. RESULTS: In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant. CONCLUSIONS: Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons' ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system.

Effects of adjuvant chemotherapy in HER2-positive or triple-negative pT1ab breast cancers: a multi-institutional retrospective study.

Previous studies have reported higher recurrence rates in T1a/b N0 breast cancers characterized by high-risk biology (HER2+ or triple-negative), but the benefits of adjuvant chemotherapy in these patients have not been established. This study was designed to determine whether recurrence risk is reduced with chemotherapy and to define a group of patients most appropriate for treatment based on retrospective data. We pooled cases from two multi-institutional databases spanning the period of 1996-2010. A propensity score model adjusted unbalanced confounders between the groups treated or untreated with adjuvant chemotherapy and, in case of HER2-positive disease, with trastuzumab. Competing risk analysis was utilized to study effects of chemotherapy on cancer recurrences in the matched populations. Among the 318 patients identified, 41 % received adjuvant chemotherapy and 54 % of HER2+ patients received it with trastuzumab. The cumulative risk of recurrence at 5 years was 7.3 %. Age less than 35 years and triple-negative status were the only significant prognostic factors. Overall, administration of chemotherapy was not associated with a significant decrease in the risk of recurrence (HR 0.93, p = 0.91). The rate of recurrence in HER2+ patients who received trastuzumab was lower but not statistically significant (HR 0.50, p = 0.63). Clinical characteristics are of limited prognostic value for stratifying risk of recurrence in very small, node-negative HER2+, or triple-negative cancers. While limited by the small number of events, our analysis does not support the increasingly prevalent practice of administering adjuvant chemotherapy in this population without more accurate prognostic and predictive factors.

Early-stage breast cancer treated with 3-week accelerated whole-breast radiation therapy and concomitant boost.

PURPOSE: To report early outcomes of accelerated whole-breast radiation therapy with concomitant boost. METHODS AND MATERIALS: This is a prospective, institutional review board-approved study. Eligibility included stage TisN0, T1N0, and T2N0 breast cancer. Patients receiving adjuvant chemotherapy were ineligible. The whole breast received 40.5 Gy in 2.7-Gy fractions with a concomitant lumpectomy boost of 4.5 Gy in 0.3-Gy fractions. Total dose to the lumpectomy site was 45 Gy in 15 fractions over 19 days. RESULTS: Between October 2004 and December 2010, 160 patients were treated; stage distribution was as follows: TisN0, n = 63; T1N0, n = 88; and T2N0, n = 9. With a median follow-up of 3.5 years (range, 1.5-7.8 years) the 5-year overall survival and disease-free survival rates were 90% (95% confidence interval [CI] 0.84-0.94) and 97% (95% CI 0.93-0.99), respectively. Five-year local relapse-free survival was 99% (95% CI 0.96-0.99). Acute National Cancer Institute/Common Toxicity Criteria grade 1 and 2 skin toxicity was observed in 70% and 5%, respectively. Among the patients with ≥ 2-year follow-up no toxicity higher than grade 2 on the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic scale was observed. Review of the radiation therapy dose-volume histogram noted that ≥ 95% of the prescribed dose encompassed the lumpectomy target volume in >95% of plans. The median dose received by the heart D05 was 215 cGy, and median lung V20 was 7.6%. CONCLUSIONS: The prescribed accelerated schedule of whole-breast radiation therapy with concomitant boost can be administered, achieving acceptable dose distribution. With follow-up to date, the results are encouraging and suggest minimal side effects and excellent local control.

Postsurgical treatment of early-stage breast cancer with electronic brachytherapy: outcomes and health-related quality of life at 1 year.

OBJECTIVES: This multicenter registry followed up patients with early-stage breast cancer treated with breast-conserving surgery and electronic brachytherapy (EBT). This report provides 1- and 2-year updates to the initial publication. METHODS: Patients were of age 50 years or more with invasive carcinoma or ductal carcinoma in situ, tumor size ≤3 cm, and negative surgical margins. After lumpectomy, patients received EBT in 10 fractions over 5 days (34 Gy total). RESULTS: Of the 69 patients enrolled, 62 were evaluated at 1 year and 20 patients at 2 years after treatment. At 1 year, 28 (45.2%) patients reported adverse events that were possibly, probably, or definitely related to treatment. Most (90%) were grade 1: manageable and typical of radiation therapy. Four events were grade 2: induration/firmness (2), field contracture (1), and seroma (1). One event was grade 3: a draining fistula at the lumpectomy site due to residual effects of a breast infection at 1 month. No recurrences have been reported. Cosmetic ratings were excellent or good in 93.4% of patients at 1 year. Most patients (69%) were energetic most or all of the time. Most patients (69% to 98%) were not affected by individual symptoms of breast disease at 1 year. Generally patients who had an adverse event did not report the corresponding symptom on the quality-of-life questionnaire. CONCLUSIONS: This registry followed up patients with early-stage breast cancer at 1 and 2 years after breast-conserving surgery and EBT. No recurrences have been reported, and adverse effects were acceptable.

Is there a role for postmastectomy radiation therapy in ductal carcinoma in situ?

Background. DCIS treated by mastectomy ensures high local control rates. There is limited data on risk for relapse and lack of clear indication for adjuvant radiation therapy (RT). We report a retrospective review on a population of DCIS patients treated with mastectomy. The objective was to identify the overall incidence of relapse, risk factors for local recurrence, and accordingly for whom adjuvant postmastectomy RT may be considered. Methods. This is an IRB-approved retrospective study on a prospective breast cancer database. From 1997 to 2007, we identified 969 patients with diagnoses of DCIS, among them 211 breasts in 207 patients were treated with mastectomy and comprise the study group. Results. With a median followup of 55 months (4.6 years) the 10-year relapse-free survival is 97%. Two of 211 breasts (0.9%) treated with mastectomy developed a local-regional recurrence. Both the relapses were among patients defined as having <1 mm final mastectomy margin. Conclusions. The rare local relapse after mastectomy limits our ability to reliably identify risk factors for relapse. The consideration for postmastectomy RT should be based on an individualized risk evaluating surgical technique used, presence of BRCA mutation, grade and extent of tumor, and proximity of lesion to the margin of resection.