Timing of Chemotherapy and Patient-Reported Outcomes After Breast-Conserving Surgery and Mastectomy with Immediate Reconstruction.

INTRODUCTION: Receipt of chemotherapy is associated with decreased satisfaction after breast surgery, but whether timing as adjuvant versus neoadjuvant (NAC) affects patient-reported outcomes (PROs) is unclear. We examined associations between chemotherapy timing and PROs after breast-conserving surgery (BCS) and mastectomy with immediate reconstruction (M-IR). METHODS: In this retrospective cohort study of patients with stage I-III breast cancer undergoing chemotherapy between January 2017 and December 2019, we compared satisfaction with breasts (SABTR) and chest physical well-being (PWB-CHEST) between chemotherapy groups in BCS and M-IR cohorts. Median SABTR and PWB-CHEST scores (scale 0-100) were compared between chemotherapy groups at baseline and for 3 years postoperatively. Factors associated with SABTR and PWB-CHEST at 1 and 2 years were assessed with multivariable linear regression. RESULTS: Overall, 640 patients had BCS and 602 had M-IR; 210 (33%) BCS patients and 294 (49%) M-IR patients had NAC. Following BCS, SABTR was higher than baseline at all postoperative timepoints, whereas 3-year SABTR remained similar to baseline following M-IR, independent of chemotherapy timing. In both surgical cohorts, PWB-CHEST was lowest after NAC at 6 months compared with baseline but was similar to adjuvant counterparts by 3 years. NAC was not a statistically significant predictor of SABTR or PWB-CHEST in either surgical cohort on multivariable analysis. CONCLUSIONS: For patients with breast cancer who require chemotherapy, neoadjuvant versus adjuvant timing does not impact long-term PROs in this study. These findings may inform shared decision making regarding the sequence of treatment in patients with operable disease.

Invasive Lobular Carcinoma-Correlation Between Imaging and Final Pathology: Is MRI Better?

BACKGROUND: Invasive lobular carcinoma (ILC) is associated with high re-excision rates following breast-conserving surgery (BCS). The correlation between lesion size on different imaging modalities and final tumor size has not been well characterized. METHODS: A prospective database of patients with stage I-III breast cancer undergoing BCS between 2006 and 2016 was reviewed. Pearson correlation analysis was used to correlate tumor size on breast imaging to final pathology. RESULTS: Of these, 111 patients with ILC were identified. Mean lesion size was 1.93 cm for MMG, 1.61 cm for US, and 2.51 cm for MRI. Mean tumor size on surgical excision was 2.64 cm. The correlation coefficient between pathology and the different imaging modalities were as follows: MMG .17, US 0.37, and MRI .58. Actual tumor size was underestimated by 1 cm in 27.1% of MMGs, 50% of USs, and in 13.3% of MRIs. 38 patients (34.2%) underwent re-excision. No differences in re-excision rates were noted in patients with and without MRI, 30.3% vs 40.0%, respectively (P = .31). CONCLUSION: While MRI provides a better estimate of tumor size than MMG and US, the size of the tumor on imaging only weakly correlated with pathology. The use of MRI does not decrease re-excision rates.

Who Are We Missing: Does Engagement in Patient-Reported Outcome Measures for Breast Cancer Vary by Age, Race, or Disease Stage?

INTRODUCTION: Patient-reported outcome measures (PROM) are used to assess value-based care. Little is known as to whether PROM response in breast cancer reflects the diverse patient population. The BREAST-Q, a validated measure of satisfaction and quality of life, and Recovery Tracker, a postoperative assessment tool, are PROM routinely delivered to all patients undergoing breast surgery at our institution. Here we determine whether response to PROM differs by age, race, language, or disease stage. METHODS: All patients who had a breast operation between January 2020 and July 2021 were requested to complete the BREAST-Q and Recovery Tracker. Non-responders did not complete the PROM at any timepoint; responders completed 1 or more. Primary outcomes included rates of non-response versus response overall. RESULTS: Of 6374 patients identified, 5653 (88.7%) responded to either PROM [4366/4751 (91.9%) BREAST-Q; 2746/3384 (81.1%) Recovery Tracker]. On univariate analysis, non-responders were older (60 years versus 55 years, p < 0.001) and more often non-English speaking (p < 0.001), Hispanic ethnicity (p = 0.031), and Black race (p < 0.001), versus responders. On multivariate analysis, non-responders were significantly more often Black race and non-English speaking (p < 0.001). Non-English speakers were significantly less responsive among all ethnicities and races except Black race. Although breast cancer stage did not reach significance for response, patients with malignant disease and those receiving neoadjuvant chemotherapy responded more often. CONCLUSIONS: Our findings demonstrate high patient engagement using 2 different PROM following breast surgery, but suggest that PROM results may not reflect the experience of the entire breast cancer population. Care process changes based solely on PROM should consider these findings to ensure that the views of the entire spectrum of patients with breast cancer are represented.

Commission on Cancer CP3R Compliance Rates for Treatment of Patients With Triple Negative and HER2+ Breast Cancer: A National Cancer Database Analysis.

BACKGROUND: Cancer Program Practice Profile Reports (CP3R) metrics were released by the Commission on Cancer to provide standards for high-quality care. One metric is the recommendation of combination chemotherapy or chemo-immunotherapy (CIT) within 120 days of diagnosis for women under 70 with AJCC T1cN0M0 or Stage IB-III HER2+ or hormone receptor negative breast cancer ([Multi-agent chemotherapy] MAC). Our study assesses national concordance rates for MAC and CIT. METHODS: The National Cancer Database was queried from 2004-2014. RESULTS: 122,045 patients met criteria, of whom treatment for 101,800 (83.4%) patients was concordant with MAC and CIT. Treatment concordance increased from 75.7% in 2004 to 89.5% in 2014. For HER2+ patients, use of CIT treatment downtrended with progression of pathological stage, from 70.1% (stage I) to 58.1% (stage III). Mean overall survival of patients whose treatment was concordant with MAC and CIT was longer than that of patients who were non-concordant (146.6 vs 143.8 months, P <.01). On Cox regression, there was a survival benefit for concordant patients who were treated at academic hospitals (HR .89, 95% CI 0.802-.976) and had private insurance (HR .76, 95% CI 0.65-.89). CONCLUSION: Compliance with MAC and CIT has improved over the past decade and is associated with a significant improvement in overall survival.

Comparison of multiple oncotype DX® from the same patient.

For women with breast cancer in whom multiple Oncotype DX® Recurrence Scores (RS) are obtained, RS concordance utilizing current NCCN recommendations has not been evaluated. Patients with two or more RS were identified. RS were stratified by NCCN guidelines and compared for concordance. Twenty-four patients were evaluated. RS concordance varied by tumor type: 100% in the same tumor, 91.7% in multiple ipsilateral tumors, 71.4% in contralateral tumors, and 66.7% in in-breast recurrent tumors. RS concordance for multiple assays in the same patient is not high enough to omit Oncotype DX® testing for each tumor.

Contemporary Cancer Program Practice Profile Report (CP3R) Compliance Rates for Breast Cancer: A National Cancer Database Analysis.

INTRODUCTION: The Commission on Cancer (CoC) issues Cancer Program Practice Profile Reports (CP3R) that set standards for high-quality care. Three metrics for breast cancer include radiation within 1 year for women < 70 years of age receiving breast-conserving surgery, radiation within 1 year after mastectomy for women with four or more positive lymph nodes (MASTRT), and hormonal therapy within 1 year of a stage IB-III hormone receptor-positive breast cancer (HT). Our study evaluates national trends in quality metric compliance. METHODS: The National Cancer Database was queried from 2004 to 2014 to identify patients who met the criteria for the three quality metrics. National trends in compliance were compared. RESULTS: Overall, 1,094,264 patients qualified for BCSRT (n = 534,147), MASTRT (n = 66,291), or HT (n = 493,826). In 2014, 91.1% of patients met BCSRT, 88.4% met MASTRT, and 90.7% met HT. BCSRT, MASTRT, and HT compliance rates were lower in community hospitals compared with Integrated Network Cancer Programs (INCP) (BCSRT: 89.0% vs. 92.8%, p < 0.01; MASTRT: 85.5% vs. 90.6%, p < 0.01; HT: 87.3% vs. 93.7%, p < 0.01). On multivariate analysis, patients receiving care at an INCP facility [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.37-1.58] and insured patients (OR 1.70, 95% CI 1.54-1.87) had higher odds of BCSRT compliance, and minorities (OR 0.76, 95% CI 0.73-0.80) had lower odds. Similar results were seen for MASTRT and HT. CONCLUSION: In more recent years, overall compliance rates for breast cancer quality metrics of BCSRT and HT by Comprehensive Community Cancer Programs, Academic/Research Programs, and INCPs have increased to meet the 90% CoC standards, while MASTRT has regressed. Community programs were least compliant with meeting the CoC standards.

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.

Gene expression comparison between primary estrogen receptor-positive and triple-negative breast cancer with paired axillary lymph node metastasis.

The aim of this study is to characterize and compare changes in gene expression patterns of paired axillary lymph node (ALN) metastases from estrogen receptor (ER)-positive and triple-negative (TNBC) primary breast cancer (PBC). Patients with stage 2-3 PBC with macrometastasis to an ALN were selected. Gene expression of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Changes in gene expression between ER/PR-positive, HER2-negative PBC, and their paired ALN metastases were compared with TNBC and their paired ALN metastases. Fourteen pairs of ER-positive and paired ALN metastasis were analyzed. Compared with the PBC, ALN metastasis had 673 significant differentially expressed genes, including 348 upregulated genes and 325 downregulated genes. Seventeen pairs of TNBC and paired ALN metastasis were analyzed. ALN metastasis had 257 significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. When gene expression of the ALN for ER-positive PBC was compared to that of TNBC, 97 genes were upregulated in both, and 115 genes were similarly downregulated. Common upregulated genes were associated with cell death, necrosis, and homeostasis. Common downregulated genes were those of migration, degradation of extracellular matrix, and invasion. Although ER-positive PBC and TNBC have a distinct gene expression profiles and distinct changes from PBC to ALN metastases, a significant number of genes are similarly up- or downregulated. Understanding the role of these common genomic changes may provide clues to understanding the metastatic process itself.

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.

Comparison of Multiple Wire, Radioactive Seed, and Savi Scout® Radar Localizations for Management of Surgical Breast Disease.

BACKGROUND: Radioactive seed localization (RSL) and the Savi Scout® radar (SSR) are newer alternatives to wire-guided localization (WL) for nonpalpable breast lesions. OBJECTIVE: The aim of this study was to compare three localization devices when multiple devices were used for preoperative localization for breast surgery. METHODS: Between July 2017 and July 2018, 68 patients had a partial mastectomy (n = 54) or breast biopsy (n = 14) with preoperative image-guided localization using multiple wires or device placement for nonpalpable lesions. Operative timing, outcomes, and 30-day complications were evaluated. RESULTS: Overall, 41 patients (60%) had WL, 11 patients (16%) had RSL, and 16 patients (24%) had SSR localization. Fifty-four patients (79.4%) had localization of two lesions and 13 patients (19.1%) had localization of three lesions. Twenty-three patients (33.8%) had a lesion that was bracketed. There was no difference in retained biopsy clip among the groups (average 7.4%; p = 0.962). For operations performed in the hospital, there was no difference in operative time among the groups, with a median of 77.5 min (p = 0.705) or total perioperative time of 508 min (p = 0.210). Among operations with delayed start times, there was a longer average delay of 95.5 min in WL, compared with 42 min in SSR (p = 0.004). A greater volume of tissue was excised in the WL group (29.5 g WL vs. 15.9 g RSL vs. 12.1 g SSR; p = 0.022). There was no difference in positive margin rate and 30-day complications among groups. CONCLUSION: SSR and RSL can be used to localize multiple breast lesions, with no difference in positive margin rates or complications and less tissue excised compared with WL.

Walking Under the Influence : Association of Time of the Day With the Incidence and Outcomes of Intoxicated Pedestrians Struck by Vehicles.

AIM: Pedestrian fatalities commonly involve alcohol. We sought to characterize alcohol intoxication among pedestrians struck by vehicles and examine correlations between admission time and injury severity. METHODS: The Los Angeles County Trauma and Emergency Medicine Information System database was reviewed for pedestrians struck by vehicles over a 16-year period starting January 2000. Subjects aged ≥18 years with available time and day of admission were selected. Patients with available blood alcohol content (BAC) were analyzed and those with positive (+) BAC (≥ 0.01%) were compared with those with negative (-) BAC. The primary outcome was mortality. RESULT: 35 840 patients met criteria, with 12 122 (33.8%) tested for BAC. 71.2% were (+) BAC. The proportion of (+) BAC pedestrians peaked at 02:00 (48.9% of admitted pedestrians, 88.5% of BAC tested pedestrians). Patients with a (+) BAC were more likely hypotensive (3.5% vs 2.7%, P = .019) and admitted with a Glasgow Coma Scale ≤ 8 (9.4% vs 7.1%, P < .001). Overall mortality was 4.6%. Those admitted from 06:00 to 11:00 had the highest odds of mortality in (+) BAC patients (4.7%, adjusted odds ratio 3.16, adjusted P < .001). CONCLUSION: Pedestrians struck by vehicles during late hours are commonly intoxicated. These findings could help legislators to implement changes and strategies to decrease the risk and burden of injury in intoxicated pedestrians.

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.

Male Breast Cancer: 13-Year Single Institution Experience.

Due to the low incidence of male breast cancer (BC), there are few studies evaluating outcomes. We evaluated the clinicopathologic features and outcomes of male BC. Male patients with BC from January 2006 to December 2018 were identified. Of 49 patients, mean age was 64 (range 33-94) years. Of the 27 (55.1%) patients who had genetic testing, 9 (33.3%) had a Breast Cancer gene (BRCA) 1 or 2 mutation. The majority of patients had a mastectomy (n = 43/49, 87.8%) and had invasive ductal carcinoma (n = 47/49, 95.9%). 20 patients (n = 20/43, 46.5%) had positive lymph nodes. 41 (n = 41/47, 87.2%) patients had estrogen receptor positive disease. The majority of patients were pathologic stage 2 (n = 21/46, 45.7%), followed by stage 1 (n = 15/46, 32.6%), stage 3 (n = 6/46, 13.0%), and stage 4 (n = 4/46, 8.7%). Eight patients had the 21-gene recurrence score performed. Of patients with stage 1-3 BC, 10 (n = 10/43, 23.3%) patients had recurrence. With median follow-up of 4.1 (range .6-10.6) years, 5-year overall survival was 82.9% and 5-year disease-free survival was 65.9%. In conclusion, our cohort of patients with male BC had a high incidence of BRCA mutations and most commonly had high-grade estrogen positive stage 2 tumors. Breast conserving surgery was utilized in 4% of patients and genomic testing utilized in 55% of patients.

Thirty-day postoperative morbidity in patients with breast cancer following neoadjuvant chemotherapy.

BACKGROUND: Early post-operative complications for patients having partial and total mastectomies after neoadjuvant chemotherapy have not been well defined. The objective was to compare post-operative complication rates among patients treated with partial mastectomy (PM), unilateral mastectomy (UM), and bilateral mastectomy (BM) after NAC. STUDY DESIGN: 398 patients with breast cancer who had NAC from 2008 to 2016 were identified from a prospectively maintained database. The primary outcome measure was 30-day post-operative morbidity. RESULTS: 125 patients (31.4%) underwent PM, 107 patients (26.9%) UM, and 166 (41.7%) BM. There was no significant difference among the 3 groups with respect to histology (ductal: 96.0% PM, 88.8% UM, 92.6% BM, p = 0.161). Groups were similar with respect to estrogen receptor positivity (overall 58.8%, p = 0.331) and triple negative biomarker status (overall 23.9%, p = 0.559). The PM group had a higher rate of HER2 positive disease (n = 58, 47.5%, p = 0.012). Patients who underwent PM had a lower clinical T Stage at presentation (p=<0.001), fewer axillary lymph node dissections (n = 32, 25.6%, p=<0.001), and a higher rate of pathologic complete response (n = 48, 38.4%, p = 0.037) compared with patients who underwent mastectomies. Overall, 52 patients (13.1%) had a complication within the 30 day post-operative period. 30-day complication rates were significantly higher in the BM group compared to the PM group: 6.4% (n = 8) for PM, 12.2% (n = 13) for UM, and 18.7% (n = 31) for BM, (p = 0.008). 30-day readmission rates were significantly higher in the BM group compared to the PM group (overall 4.5%; 0.8% PM, 2.8% UM, 8.4% BM, p = 0.004). CONCLUSION: Bilateral mastectomy is associated with higher rates of 30-day morbidity and re-admissions compared to partial mastectomy, but not unilateral mastectomy in patients who received neoadjuvant chemotherapy.

Impact of Resident and Fellow Participation on Surgical Outcomes in Breast Conserving Surgery for Invasive Breast Cancer.

OBJECTIVE: Few studies examine the impact of surgical trainee involvement on tumor-free margins in breast conserving surgery (BCS). Our objective was to investigate the impact of resident and fellow involvement on positive margins rates following BCS for invasive breast cancer (BC). DESIGN: We identified female patients who had BCS for BC between January 2005 to December 2015. SETTING: Tertiary care hospital. PARTICIPANTS: Around 1089 patients were identified from a prospectively maintained database. RESULTS: Of 1089 patients, mean age was 63 (range 43-99) years. Around 768 patients (70.1%) required preoperative localization, and 328 patients (29.9%) had a palpable cancer. Nonpalpable cancers had a smaller volume of specimen tissue excised (p = 0.0005) compared to palpable cancers, and no significant difference was observed in the positive margin rate between the nonpalpable group compared to the palpable group (24.7% nonpalpable vs. 25.3% palpable, p = 0.88). Nonpalpable cancer positive margin rates were 23.9% (n = 102/427) for cases performed by an attending surgeon, 25.0% (n = 15/60) with a junior resident (PGY 2-3), 28.6% (n = 8/28) with a senior resident (PGY 4-5), and 25.7% (n = 65/253) with a fellow, which were not statistically significant (p = 0.89). Palpable cancer positive margin rates were 27.6% (n = 47/170) for cases performed by an attending, 13.9% (n = 5/36) with an intern (PGY-1), 40.9% (n = 9/22) with a junior resident, 0% (n = 0/8) with a senior resident, and 23.9% (n = 22/92) with a fellow, which were also not significantly different (p = 0.07). CONCLUSION: Resident and fellow participation in BCS for BC does not appear to impact the rate of positive margins.