Examining Race and Patient-Reported Outcomes After Contralateral Prophylactic Mastectomy with Reconstruction.

BACKGROUND: Little is known regarding racial differences in satisfaction and quality of life (QOL) after contralateral prophylactic mastectomy (CPM). In this study, we aim to characterize associations between race, and postoperative satisfaction and well-being, utilizing the validated BREAST-Q patient-reported outcome measure. PATIENTS AND METHODS: Patients were eligible if they were diagnosed with stage 0-III unilateral breast cancer and underwent mastectomy with immediate reconstruction at our institution between 2016 and 2022. BREAST-Q surveys were administered in routine clinical care preoperatively and postoperatively to assess QOL. We assessed whether the relationship between race, and domains of satisfaction with breasts and psychosocial well-being differed by receipt of CPM compared with unilateral mastectomy at 6 months, 1 year, 2 years, and 3 years following reconstruction. RESULTS: Of 3334 women, 2040 (61%) underwent unilateral mastectomy and 1294 (39%) underwent CPM. Compared with White and Asian women who received CPM, Black women who underwent CPM were more likely to have higher BMI (p < 0.001), undergo autologous reconstruction (p = 0.006), and receive postmastectomy radiation (PMRT) (p < 0.001). There was no association between race and domains of satisfaction of breasts or psychosocial well-being for women who underwent unilateral mastectomy (p = 0.6 and p > 0.9, respectively) or CPM (p = 0.8 and p = 0.9, respectively). PMRT was negatively associated with both satisfaction with breasts (p < 0.001) and psychosocial well-being (p = 0.007). CONCLUSIONS: Differences in satisfaction with breasts and psychosocial well-being at 3-year follow-up were not associated with race but rather treatment variables, particularly the receipt of PMRT. Further investigations with a larger and more diverse population are needed to validate these findings.

Mutational Status is Associated with a Higher Rate of Pathologic Complete Response After Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) occurs in up to 20% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers. Whether this differs among BRCA mutation carriers is uncertain. This study compared pCR between BRCA1/2 mutation carriers and matched sporadic control subjects. METHODS: From November 2013 to January 2022, this study identified 522 consecutive women with clinical stage I to III HR+/HER2- breast cancer treated with NAC and surgery. The study matched BRCA1/2 mutation carriers 1:2 to non-carriers in terms of age, clinical tumor (cT) and nodal (cN) stage, and differentiation. Two-sample non-parametric tests compared baseline characteristics. Multivariable logistic regression assessed pCR (i.e., ypT0/ispN0) by BRCA1/2 mutational status. RESULTS: Of the 522 women (median age, 50 years), 59 had BRCA1/2 mutations, 78% of which were clinically node positive. Anthracycline-based NAC was administered to 97%. More BRCA1/2 mutation carriers were younger, had cT1 tumors, and had poorly differentiated disease. After matching, 58 BRCA1/2 mutation carriers were similar to 116 non-carriers in terms of age (p = 0.6), cT (p = 0.9), cN stage (p = 0.7), and tumor differentiation (p > 0.9). Among the mutation carriers, the pCR rate was 15.5% for BRCA1/2, 38% (8/21) for BRCA1, and 2.7% (1/37) for BRCA2 versus 7.8% (9/116) for the non-carriers (p < 0.001). After NAC, 5 (41.7%) of the 12 BRCA1 mutation carriers converted to pN0 versus 10 (37%) of the 27 BRCA2 mutation carriers and 19 (20.9%) of the 91 non-carriers (p = 0.3). In the multivariable analysis, BRCA1 mutation status was associated with higher odds of pCR than non-carrier status (odds ratio [OR] 6.31; 95% confidence interval [CI] 1.95-20.5; p = 0.002), whereas BRCA2 mutation status was not (OR 0.45; 95% CI 0.02-2.67; p = 0.5). CONCLUSIONS: This study showed that BRCA1 mutation carriers with HR+/HER2- breast cancers have a higher rate of pCR than sporadic cancers and may derive greater benefit from chemotherapy. The use of NAC to downstage these patients should be considered.

Satisfaction and Well-Being After Contralateral Prophylactic Mastectomy Among BRCA Mutation Carriers and Noncarriers: A Longitudinal Analysis of BREAST-Q Domains.

INTRODUCTION: Contralateral prophylactic mastectomy (CPM) is recommended for BRCA mutation carriers; its use in noncarriers relies on patient choice. We characterized differences in satisfaction and well-being after CPM between BRCA carriers and noncarriers. METHODS: BREAST-Q data were obtained before and after CPM with immediate reconstruction performed at a single institution from 2016 to 2022. Associations between BRCA status and satisfaction with breasts, psychosocial well-being, and sexual well-being were assessed, with adjustment for preoperative scores and relevant confounders. RESULTS: In total, 149 BRCA carriers and 842 noncarriers were included. Response rates varied over time (preoperative, 56%; 6 months, 78%; 1 year, 51%; 2 years, 52%; 3 years, 59%). BRCA carriers were younger (p < 0.001), with a higher rate of neoadjuvant chemotherapy (p < 0.001). More noncarriers had HR+/HER2- tumors (p < 0.001) and underwent endocrine therapy (p < 0.001). Baseline satisfaction with breasts was higher among BRCA carriers (median [interquartile range] score, 70 [53-82] vs. 58 [48-70]; p = 0.006); psychosocial (p = 0.20) and sexual (p = 0.14) well-being were not significantly different between groups. BRCA carriers had a greater decrease in satisfaction with breasts (p = 0.04) and psychological well-being (p = 0.05) from baseline to 6 months; decrease in sexual well-being (p = 0.38) was not significantly different between groups. On univariate and multivariable analyses, BRCA status was not associated with satisfaction with breasts, sexual well-being, or psychosocial well-being. CONCLUSIONS: Satisfaction and well-being were similar between BRCA carriers and noncarriers treated with CPM. Relative to noncarriers, BRCA carriers experienced a greater decline in satisfaction with breasts and psychological well-being at 6 months after CPM.

Axillary Staging Is Not Justified in Postmenopausal Clinically Node-Negative Women Based on Nodal Disease Burden.

BACKGROUND: RxPONDER showed no benefit of adjuvant chemotherapy in postmenopausal women with estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer and limited nodal burden (pN1) with a recurrence score ≤ 25, suggesting that axillary staging could be omitted in cN0 patients if significant numbers of such women do not have pN2-3 disease. Here we evaluate the pN2-3 disease rate in a large cohort of postmenopausal women presenting with cN0 breast cancer. PATIENTS AND METHODS: Consecutive postmenopausal patients presenting with T1-2N0 breast cancer who underwent axillary surgery from February 2006 to December 2011 were identified. Clinicopathologic characteristics associated with pN2-3 disease were examined using chi-square or Fisher's exact tests. RESULTS: Of 3363 postmenopausal women with cT1-2N0 breast cancer (median age 58 years, IQR 48-67 years), median tumor size was 1.3 cm (IQR 0.90-1.90cm). Post-axillary staging, 2600 (77.3%) were pN0, 643 (19.1%) were pN1, and 120 (3.6%) were pN2-3. The pN2-3 disease rate did not differ across subtypes (4.4% HER2+, 3.5% HR-/HER2-, 3.5% HR+/HER2-, p = 0.70). In the subset with HR+/HER2- tumors, on multivariable analysis, age < 65 years (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.32-4.49), lymphovascular invasion (OR 5.29, 95% CI 2.72-11.2), multifocal/centric tumors (OR 3.08, 95% CI 1.79-5.32), and tumor size > 2 cm (OR 5.51, 95% CI 3.05-10.4) were significantly associated with pN2-3 nodal burden. Of 506 patients with tumors > 2 cm, 49 (9.7%) had pN2-3 disease; in the subset of 90 patients age < 65 years who had multifocal/centric tumors > 2 cm, 23 (25.6%) had pN2-3 disease. CONCLUSIONS: In postmenopausal women with cN0 disease, pN2-3 nodal burden is uncommon; omitting axillary staging would not miss a significant number of patients who might benefit from adjuvant chemotherapy. Information available preoperatively indicating a higher risk of nodal disease such as younger age and large, multifocal tumors should be considered in the multidisciplinary management of the axilla.

Is Nodal Clipping Beneficial for Node-Positive Breast Cancer Patients Receiving Neoadjuvant Chemotherapy?

BACKGROUND: In cN1 patients rendered cN0 with neoadjuvant chemotherapy, the false-negative rate of sentinel lymph node biopsy (SLNB) is < 10% when ≥ 3 sentinel lymph nodes (SLNs) are removed. The added value of nodal clipping in this scenario is unknown. Here we determine how often the clipped node is a sentinel node when ≥ 3 SLNs are retrieved. METHODS: We identified cT1-3N1 patients treated between 02/2018 and 10/2021 with a clipped lymph node at presentation. SLNB was performed with a standardized approach of dual-tracer mapping and retrieval of ≥ 3 SLNs. Clipped nodes were not localized; SLNs were X-rayed intraoperatively to determine clip location. Axillary lymph node dissection (ALND) was performed for any residual disease or retrieval of < 3 SLNs. RESULTS: Of 269 patients, 251 (93%) had ≥ 3 SLNs. Median age was 51 years; the majority (92%) had ductal histology; 46% were HR+/HER2-. The median number of SLNs removed was 4 (IQR 3,5). The clipped node was an SLN in 88% (220/251) of cases. Of the 31 where the clipped node was not, 13 had a positive SLN mandating ALND, and the clip was identified in the ALND specimen. In the remaining 18, where ≥ 3 negative SLNs were retrieved and an ALND was not performed, the clip was not retrieved, with no axillary failures in this group (median follow-up: 55 months). CONCLUSION: When the SLNB procedure is optimized with dual tracer and retrieval of ≥ 3 SLNs, the clipped node is an SLN in the majority of cases, suggesting that failure to retrieve the clipped node should not be an indication for ALND.

Higher risk tumor features are not associated with higher nodal stage in patients with estrogen receptor-positive, node-positive breast cancer.

INTRODUCTION: Studies support omission of axillary lymph node dissection (ALND) for patients with sentinel node-positive disease, with ALND recommended for patients who present with clinically positive nodes. Here, we evaluate patient and tumor characteristics and pathologic nodal stage of patients with estrogen receptor-positive (ER +) breast cancer who undergo ALND to determine if differences exist based on nodal presentation. MATERIALS AND METHODS: Retrospective chart review from 2010 to 2019 defined three groups of patients with ER + breast cancer who underwent ALND for positive nodes: SLN + (positive node identified at SLN biopsy), cNUS (abnormal preoperative US and biopsy), and cNpalp (palpable adenopathy). Patients who received neoadjuvant chemotherapy or presented with axillary recurrence were excluded. RESULTS: Of 191 patients, 94 were SLN + , 40 were cNUS, and 57 were cNpalp. Patients with SLN + compared with cNpalp were younger (56 vs 64 years, p < 0.01), more often pre-menopausal (41% vs 14%, p < 0.01), and White (65% vs 39%, p = 0.01) with more tumors that were low-grade (36% vs 8%, p < 0.01). Rates of PR + (p = 0.16), levels of Ki67 expression (p = 0.07) and LVI (p = 0.06) did not differ significantly among groups. Of patients with SLN + disease, 64% had pN1 disease compared to 38% of cNUS (p = 0.1) and 40% of cNpalp (p = 0.01). On univariable analysis, tumor size (p = 0.01) and histology (p = 0.04) were significantly associated with pN1 disease, with size remaining an independent predictor on multivariable analysis (p = 0.02). CONCLUSION: Historically, higher risk features have been attributed to patients with clinically positive nodes precluding omission of ALND, but when restricting evaluation to patients with ER + breast cancer, only tumor size is associated with higher nodal stage.

SAVI SCOUT® localization of metastatic axillary lymph node prior to neoadjuvant chemotherapy for targeted axillary dissection: a pilot study.

PURPOSE: In clinically node-positive breast cancer, axillary staging after neoadjuvant chemotherapy (NAC) is optimized with targeted axillary dissection (TAD), which includes removal of the biopsy-proven metastatic lymph node (LN) in addition to sentinel lymph nodes (SLN). Localization of the clipped node is currently performed post-NAC; however, technical limitations can make detection and localization of the treated LN challenging. We prospectively evaluated the feasibility of localizing the metastatic LN with a SAVI SCOUT® reflector (SAVI) prior to NAC for targeted removal at surgery. METHODS: Twenty-five patients with stage 2/3 breast cancer underwent ultrasound-guided localization of the biopsy-proven LN with SAVI prior to NAC. After NAC, patients with clinical response underwent TAD. Primary outcome measures were rate of successful localization, days between insertion of SAVI and axillary surgery, frequency of retrieval of clipped node, and frequency of SAVI-LN as SLN. RESULTS: After NAC, 23/25 (92%) had clinical axillary down-staging and underwent TAD. Two patients with persistent palpable axillary disease underwent ALND for initial staging. Axillary surgery was performed at an average of 141 days post-SAVI insertion and the SAVI was successfully retrieved in all cases. Among 23 patients undergoing TAD, the SAVI was retrieved within a LN in all patients, whereas clip migration was observed in two patients. The median SLN removed was 4, and SAVI-LN was SLN in 22/23 patients. Axillary pCR rate was 44%. CONCLUSION: Localizing a metastatic LN with SAVI reflector prior to NAC for targeted removal at surgery is feasible and may provide technical and logistical advantages over axillary localization post-NAC. CLINICAL TRIAL REGISTRY: Clinical trials.gov identifier: NCT03411070.

Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy.

INTRODUCTION: Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of biomarker [hormone receptor (HR) and HER2] change and its effect on disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: A total of 303 patients treated with NAT from 2008 to 2016 were identified from a prospective database. Biomarker status at diagnosis was determined and retested after NAT in patients with RD. DFS and OS were compared among three groups: no biomarker change, clinically insignificant change in either ER or PR without alteration in HR status, and clinically significant change in at least one biomarker with resultant change in HR or HER2 status. Subgroups with no change and HR change were examined [HR+HER2- no change, triple negative (TN) no change, HR+HER2- to TN, TN to HR+HER2]. RESULTS: Overall, 61.4% of patients had RD. Of these, 32.8% had changes in at least one biomarker. At median follow up of 5.48 years, no biomarker change was associated with improved DFS compared with changes in HR or HER2 status (p = 0.043). In addition, no biomarker change (p = 0.005) and clinically insignificant changes in biomarker status (p = 0.019) were associated with improved OS compared with clinically significant changes in HR or HER2 status. Among subgroups, HR+HER2- to TN was associated with worse DFS (p = 0.029) and OS (p = 0.008) compared with HR+HER2- no change. CONCLUSIONS: Among those with RD, biomarker status change was common and impacted survival in subgroups of HR+ or TN disease. Retesting biomarkers after NAT has prognostic implications.

National trends and predictors of mastectomy with immediate breast reconstruction.

PURPOSE: This study aimed to evaluate national trends in utilization, resource use, and predictors of immediate breast reconstruction (IR) after mastectomy. METHODS: The 2005-2014 National Inpatient Sample database was used to identify adult women undergoing mastectomy. IR was defined as any reconstruction during the same inpatient stay. Multivariable regression models were utilized to identify factors associated with IR. RESULTS: Of 729,340 patients undergoing mastectomy, 41.3% received IR. Rates of IR increased from 28.2% in 2005 to 58.2% in 2014 (NP-trend<0.001). Compared to mastectomy alone, IR was associated with increased length of stay (2.5 vs. 2.1 days, P < 0.001) and hospitalization costs ($17,628 vs. $8,643, P < 0.001), which increased over time (P < 0.001). Predictors of IR included younger age, fewer comorbidities, White race, private insurance, top income quartile, teaching hospital designation, high mastectomy volume, and performance of bilateral mastectomy. CONCLUSION: Mastectomy with IR is increasingly performed with resource utilization rising at a steady pace. Our study points to persistent sociodemographic and hospital level disparities associated with the under-utilization of IR. Efforts are needed to alleviate disparities in IR.

"Going Flat" After Mastectomy: Patient-Reported Outcomes by Online Survey.

BACKGROUND: The Going Flat movement aims to increase awareness and acceptance of mastectomy alone as a viable option for patients. Little is known about motivations and satisfaction with surgical outcomes in this population. METHODS: An online survey was administered to 931 women who had a history of uni- or bilateral mastectomy for treatment of breast cancer or elevated breast cancer risk without current breast mound reconstruction. Satisfaction with outcome and surgeon support for the patient experience were characterized using 5-level scaled scores. RESULTS: Mastectomy alone was the first choice for 73.7% of the respondents. The top two reasons for going flat were desire for a faster recovery and avoidance of a foreign body placement. Overall, the mean scaled satisfaction score was 3.72 ± 1.17 out of 5. In the multivariable analysis, low level of surgeon support for the decision to go flat was the strongest predictor of a satisfaction score lower than 3 (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.59-5.72; p < 0.001). Dissatisfaction also was more likely among respondents reporting a body mass index (BMI) of 30 kg/m2 or higher (OR, 2.74; 95% CI, 1.76-4.27; p < 0.001) and those undergoing a unilateral procedure (OR, 1.99; 95% CI, 1.29-3.09; p = 0.002). Greater satisfaction was associated with receiving adequate information about surgical options (OR, 0.48; 95% CI, 0.32-0.69; p < 0.0001) and having a surgeon with a specialized breast surgery practice (OR, 0.56; 95% CI, 0.38-0.81; p = 0.002). CONCLUSIONS: Most patients undergoing mastectomy alone are satisfied with their surgical outcome. Surgeons may optimize patient experience by recognizing and supporting a patient's decision to go flat.

Incidental radiologic findings in breast cancer patients who undergo staging prior to neo-adjuvant chemotherapy.

NCCN guidelines discourage the use of staging imaging for newly diagnosed patients with early breast cancer (BC). When performed, incidental radiologic findings of uncertain significance are often encountered. The purpose of this study was to compare incidental findings seen on staging imaging with distant recurrence in patients undergoing neo-adjuvant chemotherapy (NAC). 396 patients with BC who had NAC from 2008 to 2016 were identified from a prospectively maintained data base. Staging imaging was reviewed. Of 396 patients with BC treated with NAC, patients with a positive PET/CT for metastatic disease (n = 36, 9.1%), those that did not undergo staging imaging (n = 49, 12.4%), or those that did not have a reported incidental finding (n = 49, 12.4%) were excluded from analysis. Of the 262 patients who met criteria, mean age was 50 years (range: 26-88). 201 (76.7%) patients had stage I-II cancer, and 61 (23.3%) patients had stage III cancer. Overall, 146 (55.7%) patients had an incidental finding on imaging. 90 (34.4%) patients had one finding, 42 (16.0%) patients had two, and 14 (5.3%) patients had three or more findings. The majority of incidental findings were seen in the ovary/uterus (29.7%), followed by lung (18.4%), liver (10.3%), and bone (9.0%). 5 (3.4%) patients had additional imaging performed. At mean follow-up of 3.7 years (range: 0.7-10.8), 43 (15.6%) patients had a distant recurrence. Of these patients, only 5 (1.9%) patients had distant metastasis in the same organ that was initially thought to be an incidental finding. Our results suggest that breast cancer patients with incidental findings on preoperative staging imaging are unlikely to be indicative of sites for future metastasis.

Assessing the Burden of Nodal Disease for Breast Cancer Patients with Clinically Positive Nodes: Hope for More Limited Axillary Surgery.

BACKGROUND: Omission of axillary lymph node dissection (ALND) is accepted for patients with one or two positive sentinel nodes, and studies are focusing on clinically node-positive patients who have been downstaged with neoadjuvant chemotherapy (NAC). Evidence is lacking for patients with positive nodes who undergo surgery upfront. These patients are assumed to have a higher burden of nodal disease such that ALND remains the standard of care. METHODS: Patients who underwent ALND for breast cancer between 2010 and 2019 at the authors' institution were retrospectively identified. Those with clinical N1 disease were included in the study. Patients who received NAC and those who had surgery for sentinel node positive disease or axillary recurrence were excluded. Clinical and pathologic factors associated with nodal stage were evaluated. RESULTS: Of 111 patients who met the inclusion criteria, 61.3% had a palpable node on exam, and 41.4% ultimately had pN1 disease. Most of the tumors were estrogen receptor (ER)-positive (91.5%), and 21.7% of the tumors were invasive lobular cancers. Lobular histology, tumor size, and metastasis size were associated with higher nodal stage. In the multivariable analysis, the patients with nodal metastasis larger than 10 mm had significantly lower odds of having pN1 disease (odds ratio 0.12; 95% confidence interval 0.02-0.69; p = 0.02). In a subset analysis of patients with palpable nodes, tumor size and histology remained significantly associated with nodal stage. CONCLUSION: More than 40% of breast cancer patients with clinically positive nodes had minimal nodal disease (pN1) at surgery. Additionally, palpable nodes on exam did not predict higher nodal stage. A subset of patients with clinically positive nodes may be identified who can potentially be spared the morbidity of ALND.

How patients experience endocrine therapy for breast cancer: an online survey of side effects, adherence, and medical team support.

PURPOSE: Many patients with hormone receptor-positive (HR+) breast cancer do not adhere to endocrine therapy (ET), and treatment-related side effects are often discussed by participants in online breast cancer forums. Our aim was to survey this unique group of patients about their ET-related experiences. METHODS: We partnered with patients active in breast cancer social media communities to develop a survey assessing ET-related side effects and medical team communication. Patients with a history of HR+ breast cancer who had received a recommendation to take ET were eligible to participate in the anonymous, online survey. RESULTS: Respondents included 2353 women and 54 men. Aromatase inhibitors were the most commonly used medication. Side effects were reported by 91.2%, were more often experienced by women than men (p < 0.001), and were primarily related to medication type. Approximately one-third of respondents discontinued therapy early. While most felt supported by their medical team, 31.5% reported that their side effects were dismissed or minimized. Survey respondents most frequently reported that a healthy diet and exercise, yoga/acupuncture, and vitamins/supplements were helpful in managing ET-related side effects. CONCLUSIONS: ET-related side effects are very common, and one-third discontinued treatment early. Lifestyle changes and complementary therapies can be important tools for side effect management. One-third of patients did not feel that their side effects were taken seriously. IMPLICATIONS FOR CANCER SURVIVORS: This is the largest survey of ET use by participants in online breast cancer communities. Further research is needed to identify strategies to improve treatment adherence and to better manage ET-related side effects.

Can Radiologic Tumor Size Following Neoadjuvant Therapy Reliably Guide Tissue Resection in Breast Conserving Surgery in Patients with Invasive Breast Cancer?

Optimum tissue resection volume for patients with invasive breast cancer undergoing breast conserving surgery following neoadjuvant therapy (NAT) is not known. We compared positive margin and in-breast tumor recurrence (IBTR) between 2 groups that were created based on radiologic tumor size (RTS (cm3)) at diagnosis, RTS post-NAT, and volume of tissue resected (VTL): Pre-NAT group, patients with VTL closer to RTS at diagnosis, and post-NAT group, patients with VTL closer to post-NAT RTS. 82 patients with 84 breast cancers treated with NAT between 2007 and 2017 who had pre- and post-NAT imaging were identified from a prospectively maintained database. RTS at diagnosis, RTS post-NAT, and VTL were determined. Clinical and treatment characteristics, IBTR, and disease-free survival (DFS) were compared between pre-NAT (n = 51) and post-NAT (n = 33) groups. Compared to post-NAT patients, pre-NAT patients had smaller RTS at presentation (9.2 vs. 33.5 cm3, P < .001) and post-NAT (1.2 vs. 8.2 cm3, P = .024). At median follow-up of 4 years, there were no differences between groups in pathologic tumor size, positive margin rate, adjuvant therapy, IBTR, or DFS. Resection volumes that matched RTS on post-NAT imaging were not associated with increased positive margins or IBTR. It may be appropriate to use post-NAT imaging to guide lumpectomy volume.