Guideline-Concordant Surgical Care for Lobular Versus Ductal Inflammatory Breast Cancer.

INTRODUCTION: Quality of surgical care is understudied for lobular inflammatory breast cancer (IBC), which is less common, more chemotherapy-resistant, and more mammographically occult than ductal IBC. We compared guideline-concordant surgery (modified radical mastectomy [MRM] without immediate reconstruction following chemotherapy) for lobular versus ductal IBC. METHODS:  Female individuals with cT4dM0 lobular and ductal IBC were identified in the National Cancer Database (NCDB) from 2010-2019. Modified radical mastectomy receipt was identified via codes for "modified radical mastectomy" or "mastectomy" and "≥10 lymph nodes removed" (proxy for axillary lymph node dissection). Descriptive statistics, chi-square tests, and t-tests were used. RESULTS: A total of 1456 lobular and 10,445 ductal IBC patients were identified; 599 (41.1%) with lobular and 4859 (46.5%) with ductal IBC underwent MRMs (p = 0.001). Patients with lobular IBC included a higher proportion of individuals with cN0 disease (20.5% lobular vs. 13.7% ductal) and no lymph nodes examined at surgery (31.2% vs. 24.5%) but were less likely to be node-negative at surgery (12.7% vs. 17.1%, all p < 0.001). Among those who had lymph nodes removed at surgery, patients with lobular IBC also had fewer lymph nodes excised versus patients with ductal IBC (median [interquartile range], 7 (0-15) vs. 9 (0-17), p = 0.001). CONCLUSIONS: Lobular IBC patients were more likely to present with node-negative disease and less likely to be node-negative at surgery, despite having fewer, and more frequently no, lymph nodes examined versus ductal IBC patients. Future studies should investigate whether these treatment disparities are because of surgical approach, pathologic assessment, and/or data quality as captured in the NCDB.

Temporal Trends and Factors Associated with Receipt of Post-mastectomy Radiation After Neoadjuvant Chemotherapy in Women with cT3 Breast Cancer.

INTRODUCTION: Given the potential impact of increasingly effective neoadjuvant chemotherapy (NACT) on post-mastectomy radiotherapy (PMRT) recommendations, we examined temporal trends in post-NACT PMRT for cT3 breast cancer. METHODS: We identified women ≥ 18 years in the National Cancer Database (NCDB) diagnosed 2004-2019 with cT3N0-1M0 breast cancer treated with chemotherapy and mastectomy. Multivariable logistic regression and Cox proportional hazards models were used to estimate associations between pathologic NACT response [complete response (CR), partial response (PR), or no response (NR); or disease progression (DP)] and PMRT and between PMRT and overall survival (OS), respectively. RESULTS: We identified 39,901 women (Asian/Pacific Islander 1731, Black 5875, Hispanic 3265, White 27,303). Among cN0 patients with CR, PMRT rates declined from 67% in 2004 to 35% in 2019 but remained unchanged for patients with DP. Relative to NR, CR [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.29-0.46] and PR (OR 0.44, 95% CI 0.36-0.55) in cN0 patients were associated with lower odds of PMRT while DP (OR 1.33, 95% CI 1.05-1.69) was associated with higher odds. Among cN1 patients, PMRT rates decreased from 90% to 73% for CR between 2005 and 2019 and increased from 76% to 82% for DP between 2004 and 2019. Relative to NR, CR (OR 0.78, 95% CI 0.63-0.95) was associated with lower odds of PMRT while DP (OR 1.93, 95% CI 1.58-2.37) was associated with higher odds. PMRT was associated with improved OS among cN1 patients (hazard ratio (HR) 0.77, 95% CI 0.67-0.88). CONCLUSION: CR was associated with decreased PMRT receipt over time, while temporal trends following PR and DP differed by cN status, suggesting that nodal involvement guided PMRT receipt more than in-breast disease.

Impact of Patient Comorbidities on Presentation Stage of Breast and Colon Cancers.

BACKGROUND: While patients with multiple comorbidities may have frequent contact with medical providers, it is unclear whether their healthcare visits translate into earlier detection of cancers, specifically breast and colon cancers. METHODS: Patients diagnosed with stage I-IV breast ductal carcinoma and colon adenocarcinoma were identified from the National Cancer Database and stratified by comorbidity burden, dichotomized as a Charlson Comorbidity Index (CCI) Score of <2 or ≥2. Characteristics associated with comorbidities were analyzed by univariate and multivariate logistic regression. Propensity-score matching was performed to determine the impact of CCI on stage at cancer diagnosis, dichotomized as early (I-II) or late (III-IV). RESULTS: A total of 672,032 patients with colon adenocarcinoma and 2,132,889 with breast ductal carcinoma were included. Patients with colon adenocarcinoma who had a CCI ≥ 2 (11%, n = 72,620) were more likely to be diagnosed with early-stage disease (53% vs. 47%; odds ratio [OR] 1.02, p = 0.017), and this finding persisted after propensity matching (CCI ≥ 2 55% vs. CCI < 2 53%, p < 0.001). Patients with breast ductal carcinoma who had a CCI ≥ 2 (4%, n = 85,069) were more likely to be diagnosed with late-stage disease (15% vs. 12%; OR 1.35, p < 0.001). This finding also persisted after propensity matching (CCI ≥ 2 14% vs. CCI < 2 10%, p < 0.001). CONCLUSIONS: Patients with more comorbidities are more likely to present with early-stage colon cancers but late-stage breast cancers. This finding may reflect differences in practice patterns for routine screening in these patients. Providers should continue guideline directed screenings to detect cancers at an earlier stage and optimize outcomes.

Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

New Operative Reporting Standards: Where We Stand Now and Opportunities for Innovation.

BACKGROUND: The American College of Surgeons Commission on Cancer's (CoC) new operative standards for breast cancer, melanoma, and colon cancer surgeries will require that surgeons provide synoptic documentation of essential oncologic elements within operative reports. Prior to designing and implementing an electronic tool to support synoptic reporting, we evaluated current documentation practices at our institution to understand baseline concordance with these standards. METHODS: Applicable procedures performed between 1 January 2018 and 31 December 2018 were included. Two independent reviewers evaluated sequential operative notes, up to a total of 100 notes, for documentation of required elements. Complete concordance (CC) was defined as explicit documentation of all required CoC elements. Mean percentage CC and surgeon-specific CC were calculated for each procedure. Interrater reliability was assessed via Cohen's kappa statistic. RESULTS: For sentinel lymph node biopsy, mean CC was 66% (n = 100), with surgeon-specific CC ranging from 6 to 100%, and for axillary dissection, mean CC was 12% (n = 89) and surgeon-specific CC ranged from 0 to 47%. The single surgeon performing melanoma wide local excision had a mean CC of 98% (n = 100). For colon resections, mean CC was 69% (n = 96) and surgeon-specific CC ranged from 39 to 94%. Kappa scores were 0.77, 0.78, -0.15, and 0.78, respectively. CONCLUSIONS: We identified heterogeneity in current documentation practices. In our cohort, rates of baseline concordance varied across surgeons and procedures. Currently, documentation elements are interspersed within the operative report, posing challenges to chart abstraction with resulting imperfect interrater reliability. This presents an exciting opportunity to innovate and improve compliance by introducing an electronic synoptic documentation tool.

Effectiveness of a Short Duration of Neoadjuvant Endocrine Therapy in Patients with HR+ Breast Cancer-An NCDB Analysis (2004-2016).

BACKGROUND: National medical/surgical organizations have recommended the use of neoadjuvant endocrine therapy (NET) to bridge surgery delay of weeks to months for patients with hormone receptor positive (HR+) breast cancer during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The effects of NET of varying durations on pathologic response are unclear. Using the National Cancer Database (NCDB), we evaluated objective response to short (< 9 weeks), moderate (9-27 weeks), and long (> 27 weeks) duration of NET. PATIENTS AND METHODS: The study cohort included female patients diagnosed with nonmetastatic invasive HR+ breast cancer, stratifying by those who received NET versus no NET between 2004 and 2016. Pathologic response was grouped into four categories (complete, downstaged, stable, upstaged) by comparing clinical and pathologic staging data. Objective response to NET included complete, downstaged, and stable pathologic response. Clinical characteristics were compared using χ2 and analysis of variance (ANOVA) tests. Multivariable logistic regression was used to determine factors associated with NET use and objective response according to NET duration. RESULTS: A minority (1.2%) received NET in our cohort. Factors associated with NET use included older age, non-Black patients, more advanced clinical stage, higher comorbidity score, government insurance, and lobular histology. Objective response rate (ORR) was 56.7%, 52.1%, and 49.0% after short, moderate, and long NET duration, respectively. CONCLUSION: Short NET duration did not result in an inferior ORR. Future study to evaluate the interaction between surgery delay and NET use on clinical outcome will provide insights into the safety of NET to bridge potential surgery delay in patients with HR+ breast cancer.

Immediate Breast Reconstruction for Inflammatory Breast Cancer: Trends in Use and Clinical Outcomes 2004-2016.

INTRODUCTION: National guidelines specify against immediate breast reconstruction (IBR) among inflammatory breast cancer (IBC) patients. However, limited data exist regarding this practice. We report practice patterns and oncologic outcomes among nonmetastatic IBC patients receiving trimodality therapy, with or without IBR. METHODS: Using the National Cancer Database, we identified nonmetastatic IBC patients treated with trimodality therapy from 2004 to 2016. Primary outcome was overall survival (OS), assessed on unadjusted analysis using Kaplan-Meier estimates and on adjusted analysis using multivariable Cox proportional hazards and inverse probability weighting (IPW) models. OS analysis was also conducted with propensity score matched (PSM) cohorts. Secondary outcomes included IBR utilization rates, time to postmastectomy radiotherapy (PMRT), and surgical outcomes. RESULTS: 6589 women were included, including 5954 (90.4%) non-reconstructed and 635 (9.6%) IBR. Among IBR recipients, 250 (39.4%) underwent autologous reconstruction, 171 (26.9%) underwent implant-based reconstruction, and 214 (33.7%) unspecified. IBR utilization increased from 6.3% to 10.1% from 2004 to 2016 at a 4% average annual growth rate (P < 0.001). Median follow-up was 43 and 45 months for IBR and non-reconstructed patients, respectively (P = 0.29). On Cox multivariable analysis, IBR was associated with improved OS (HR 0.63, 95% CI 0.44-0.90, P = 0.01), but this association was not significant on IPW analysis (P = 0.06). In PSM cohorts, this association remained significant (HR 0.60, 95% CI 0.40-0.92, P = 0.02). Margin status, time to PMRT, 30-day readmission, and 30-/90-day mortality did not differ between groups (all P > 0.05). CONCLUSION: Although not endorsed by national guidelines, IBR is increasing among IBC patients; however, more granular data are needed to determine oncologic safety.

Utility of Oncotype DX in Male Breast Cancer Patients and Impact on Chemotherapy Administration: A Comparative Study with Female Patients.

BACKGROUND: Use of the Oncotype DX recurrence score (RS) has been widely adopted in women with early-stage hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER-) breast cancer (BC). Validation studies on the use of RS in male BC (MBC) are lacking. OBJECTIVE: The aim of this study was to identify the utilization of RS and association with chemotherapy recommendations in early-stage MBC compared with female BC (FBC). METHODS: Using the National Cancer Database (NCDB), a retrospective review was performed for patients with T1/T2, node-negative, HR+/HER2- BC between 2010 and 2014. Patients were stratified by demographics, tumor characteristics, RS, and chemotherapy use comparing MBC with FBC over the allotted time period. RESULTS: A total of 358,497 patients-3068 (0.8%) males and 355,429 (99.1%) females-met the inclusion criteria. A smaller proportion of MBC patients received RS testing compared with FBC patients (32% vs. 35%, p < 0.001). Male patients who had RS were younger, had T2 tumors, lymphovascular invasion, and private insurance. The distribution of RS was similar in both groups. Only 4% of MBC patients with low RS received adjuvant chemotherapy, compared with 4.9% of FBC patients. Overall chemotherapy rates were similar in MBC and FBC patients. CONCLUSIONS: Our results showed that RS has not been completely embraced in the management of MBC, although when performed in MBC, chemotherapy recommendations vary based on RS. Whether the use of RS affects the clinical outcomes of MBC is unknown. A prospective registry would help clarify and evaluate the impact of RS on clinical outcomes in MBC.

Does time to adjuvant chemotherapy (TTC) affect outcomes in patients with triple-negative breast cancer?

PURPOSE: A recent study reported that time to adjuvant chemotherapy (TTC) > 30 days was significantly associated with worse OS and DFS in triple-negative breast cancer (TNBC). Earlier studies, however, found that worse outcomes were associated with TTC > 60 days or > 90 days. As the trend for mastectomy with reconstruction continues to rise, TTC of < 30 days is often not feasible due to wound-healing issues in some of these patients. To elucidate the impact of TTC, we sought to evaluate the clinical outcomes associated with TTC in a contemporary cohort treated for TNBC at a single institution. METHODS: A single-institution database was queried to identify nonmetastatic TNBC patients who received adjuvant chemotherapy from 2009 to 2018. TTC was defined as interval between date of surgery and adjuvant chemotherapy start date. Median TTC was used to divide our cohort into four quartiles; ≤ 31, 32-42, 43-56, and > 56 days. Logrank, Kaplan-Meier, and inverse probability weighting (IPW) tests were used to analyze disease-free (DFS) and overall survival (OS). RESULTS: The mean TTC of our study cohort (n = 724) was 48 days (median TTC = 42 days). Black race, mastectomy without adjuvant radiation, and mastectomy with immediate reconstruction were associated with delayed TTC (all p-values < 0.01). In multivariate IPW analysis, TTC > 56 (n = 173) days did not impact DFS or OS compared to TTC ≤ 31 (n = 198) days (p = 0.27 and p = 0.21, respectively). Similar results were seen during subgroup analysis for groups identified as higher risk for delayed TTC. CONCLUSION: Our results demonstrated that TTC was not significant or significantly associated with DFS or OS in patient receiving chemotherapy for operable TNBC. Our results were reassuring for patients electing mastectomy with immediate reconstruction, who may experience a longer TTC.

Quality of life and sexual well-being after nipple sparing mastectomy: A matched comparison of patients using the breast Q.

BACKGROUND: Nipple sparing mastectomy (NSM) is considered safe for select patients. Our objective was to examine quality of life (QOL) and satisfaction for NSM compared with skin sparing mastectomy (SSM). We aimed to evaluate these using the BREAST-Q. METHODS: After IRB approval, we analyzed patients who underwent NSM and reconstruction between July 2010-June 2015. NSM patients were matched with those after SSM based on age, race, and body mass index. Telephone interviews were prospectively conducted using the BREAST-Q Mastectomy Postoperative Module. Bivariate analysis and a paired samples t-test were performed. RESULTS: We identified 43 patients meeting our inclusion criteria with a response rate 60% (N = 26). NSM and SSM patients were matched well in age (P = 1.00), race (P = 1.00), and Body Mass Index (P = 0.99). There were no significant differences in stage, estrogen and progesterone status, HER2 expression, reconstruction type and radiation. Mean BREAST-Q scores did not vary between NSM and SSM in regards to satisfaction with breasts (P = 0.604), psychosocial well-being (P = 0.146), physical well-being (P = 0.121), and satisfaction with surgeon (P = 0.170). Sexual well-being was significantly higher in NSM patients (P = 0.011). CONCLUSION: NSM provides patients with favorable results in psychosocial, sexual, and physical well-being and overall satisfaction. Sexual well-being showed significant improvement for NSM.

Prescription and adherence to lymphedema self-care modalities among women with breast cancer-related lymphedema.

PURPOSE: To profile the prescription for and adherence to breast cancer-related lymphedema (BCRL) self-care modalities among breast cancer (BrCa) survivors with BCRL in a 12-month randomized weightlifting trial. METHODS: We developed a questionnaire that assessed prescription for and adherence to 10 BCRL self-care modalities that included physical therapy exercise, pneumatic compression pump, medication, lymphedema bandaging, arm elevation, self-administered lymphatic drainage, therapist-administered lymphatic drainage, compression garments, skin care, and taping. We measured prescription for and adherence to BCRL self-care modalities at baseline, 3, 6, and 12 months. Longitudinal logistic regression was used to estimate the odds ratio (OR) and 95 % confidence interval (95 % CI) associated with prescription for and adherence to BCRL modalities over time. RESULTS: This study included 141 BrCa survivors with BCRL. Women were prescribed an average of 3.6 ± 2.1 BCRL self-care modalities during the study. The prescription for therapist-administered lymphatic drainage (OR = 0.92, 95 % CI 0.88-0.96), pneumatic compression pump use (OR = 0.94, 95 % CI 0.89-0.98), and bandaging (OR = 0.96, 95 % CI 0.93-0.99) decreased over 12 months of follow-up. No other prescribed BCRL self-care modalities changed during the study. Over 12 months, the average adherence to all BCRL self-care modalities varied with 13, 24, 32, and 31 % of women reporting <25, 25-49, 50-74, and ≥75 % adherence, respectively. Over 12 months, there was a noticeable change from high to low adherence in self-administered lymphatic drainage, such that there was a 15 % increased likelihood of adherence <25 % compared to ≥75 % (OR = 1.15 (95 % CI 1.05-1.26); p = 0.002). The adherence patterns of all other modalities did not change over follow-up. CONCLUSIONS: Our findings suggest the prescription for BCRL self-care modalities is variable. The average adherence to BCRL self-care was non-optimal. Future research is necessary to prepare BrCa survivors with the knowledge, skills, abilities, and resources necessary to care for this lifelong condition.

Five-Year Outcomes of a Phase 1/2 Trial of Accelerated Partial Breast Irradiation Using Proton Therapy for Women With Stage 0-IIA Breast Cancer.

Purpose: We report the results of a phase 1/2 trial of external beam partial breast radiation using proton therapy. Methods and Materials: Eligible patients included stage 0-IIA breast cancer pTis-T2, N0, and size ≤3 cm. Proton beam radiation was used to deliver 3.85 Gy twice daily to 38.5 Gy. The phase 1 portion determined feasibility based on criteria of successful plan creation, treatment delivery, and acute toxicity grade ≥3 in ≤20% of patients. The phase 2 portion had efficacy goals of acute toxicity grade ≥3 in ≤20% of patients and observing physician-rated cosmesis of excellent or good >85% of patients at 2 years. Results: From April 2013 to March 2015, there were 12 patients enrolled onto the phase 1 portion, and the preplanned analysis of feasibility was met in all 4 required criteria. From July 2015 through December 2019 there were 28 patients with 29 treated breasts (1 bilateral) enrolled onto the phase 2 portion of the trial out of 45 originally planned. The trial was closed to accrual because of the coronavirus pandemic and not reopened. Thirty-eight breasts were treated with double-scattering and 3 pencil-beam scanning protons. The median follow-up of the 40 patients is 5.4 years (range, 2.3-8.6 years). There was 1 local recurrence. There was no grade ≥3 acute or late toxicity. At baseline all patients had physician-rated cosmesis good or excellent but at 2 years was excellent in 56%, good in 19%, and fair in 25%. Conclusions: Proton-accelerated partial breast irradiation delivered with a twice-daily fractionation was feasible and associated with very low acute and long-term toxicity. However, the trial did not meet goals for cosmesis outcomes and was closed prematurely. Future study is needed to determine whether pencil-beam scanning protons or different fractionation could improve these outcomes.