Long-Term Patient-Reported Arm Symptoms in Breast Cancer Survivors.

BACKGROUND: Understanding long-term arm symptoms in breast cancer survivors is critical given excellent survival in the modern era. METHODS: This cross-sectional study included patients treated for stage 0-III breast cancer at our institution from 2002 to 2012. Patient-reported arm symptoms were collected from the EORTC QLQ-BR23 questionnaire. We used linear regression to evaluate adjusted associations between locoregional treatments and the continuous Arm Symptom (AS) score (0-100; higher score reflects more symptoms). RESULTS: A total of 1126 patients expressed interest in participating and 882 (78.3%) completed the questionnaire. Mean time since surgery was 10.5 years. There was a broad distribution of locoregional treatments, including axillary lymph node dissection (ALND) in 37.1% of patients, mastectomy with reconstruction in 36.5% of patients, and post-mastectomy radiation in 38.2% of patients. Overall, 64.3% (95% confidence interval [CI] 61.1-67.4%) of patients reported no arm symptoms, 17.0% (95% CI 14.7-19.6%) had one mild symptom, 9.4% (95% CI 7.7-11.5%) had two or more mild symptoms, and 9.3% (95% CI 7.6-11.4%) reported one or more severe symptoms. Adjusted AS scores were significantly higher with ALND versus sentinel node biopsy (ß 3.5, p = 0.01), and with autologous reconstruction versus all other breast/reconstructive surgery types (ß 4.5-5.5, all p < 0.05). There was a significant interaction between axillary and breast/reconstructive surgery, with the greatest effect of ALND in those with mastectomy with implant (ß 9.7) or autologous (ß 5.7) reconstruction. CONCLUSIONS: One in three patients reported arm symptoms at a mean of 10 years from treatment for breast cancer, although rates of severe symptoms were low (<10%). Attention is warranted to the arm morbidity related to both axillary and breast surgery during treatment counseling and survivorship.

Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions.

BACKGROUND: High-risk lesions (HRL) of the breast are risk factors for future breast cancer development and may be associated with a concurrent underlying malignancy when identified on needle biopsy; however, there are few data evaluating HRLs in carriers of germline pathogenic variants (PVs) in breast cancer predisposition genes. METHODS: We identified patients from two institutions with germline PVs in high- and moderate-penetrance breast cancer predisposition genes and an HRL in an intact breast, including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular neoplasia (LN). We calculated upgrade rates at surgical excision and used Kaplan-Meier methods to characterize 3-year breast cancer risk in patients without upgrade. RESULTS: Of 117 lesions in 105 patients, 65 (55.6%) were ADH, 48 (41.0%) were LN, and 4 (3.4%) were FEA. Most PVs (83.8%) were in the BRCA1/2, CHEK2 and ATM genes. ADH and FEA were excised in most cases (87.1%), with upgrade rates of 11.8% (95% confidence interval [CI] 5.5-23.4%) and 0%, respectively. LN was selectively excised (53.8%); upgrade rate in the excision group was 4.8% (95% CI 0.8-22.7%), and with 20 months of median follow-up, no same-site cancers developed in the observation group. Among those not upgraded, the 3-year risk of breast cancer development was 13.1% (95% CI 6.3-26.3%), mostly estrogen receptor-positive (ER +) disease (89.5%). CONCLUSIONS: Upgrade rates for HRLs in patients with PVs in breast cancer predisposition genes appear similar to non-carriers. HRLs may be associated with increased short-term ER+ breast cancer risk in PV carriers, warranting strong consideration of surgical or chemoprevention therapies in this population.

Nodal positivity and systemic therapy among patients with clinical T1-T2N0 human epidermal growth factor receptor-positive breast cancer: Results from two international cohorts.

BACKGROUND: The optimal treatment strategy for patients with small human epidermal growth factor receptor 2 (HER2)-positive tumors is based on nodal status. The authors' objective was to evaluate pathologic nodal disease (pathologic lymph node-positive [pN-positive] and pathologic lymph node-positive after preoperative systemic therapy [ypN-positive]) rates in patients who had clinical T1-T2 (cT1-cT2)N0M0, HER2-positive breast cancer treated with upfront surgery or neoadjuvant chemotherapy (NAC). METHODS: Two databases were queried for patients who had cT1-cT2N0M0, HER2-positive breast cancer: (1) the Dana-Farber Brigham Cancer Center (DF/BCC) from February 2015 to October 2020 and (2) the Hospital Clinic of Barcelona and the Hospital Clinico of Valencia (HCB/HCV) from January 2012 to September 2021. The pN-positive/ypN-positive and axillary lymph node dissection (ALND) rates were compared between patients who underwent upfront surgery versus those who received NAC. RESULTS: Among 579 patients from the DF/BCC database, 368 underwent upfront surgery, and 211 received NAC; the rates of nodal positivity were 19.8% and 12.8%, respectively (p = .021). The pN-positive rates increased by tumor size (p < .001), reaching 25% for those with cT1c tumors. The ypN-positive rates did not correlate with tumor size. NAC was associated with decreased nodal positivity (odds ratio, 0.411; 95% confidence interval, 0.202-0.838), but the ALND rates were similar (22 of 368 patients [6.0%] who underwent upfront surgery vs. 18 of 211 patients [8.5%] who received NAC; p = .173). Among 292 patients from the HCB/HCV database, 119 underwent upfront surgery, and 173 received NAC; the rates of nodal positivity were 21% and 10.4%, respectively (p = .012). The pN-positive rates increased with tumor size (p = .011). The ALND rates were equivalent by treatment strategy (23 of 119 patients [19.3%] who underwent upfront surgery vs. 24 of 173 patients [13.9%] who received NAC; p = .213). CONCLUSIONS: Among patients who had cT1-cT2N0M0, HER2-positive breast cancer, approximately 20% who underwent upfront surgery were pN-positive, and the rate reached 25% for those with cT1c tumors. Given the opportunity for tailored therapy among lymph node-positive, HER2-positive patients, these data provide rationale for future analyses investigating the utility of routine axillary imaging in patients with HER2-positive breast cancer.

Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

BACKGROUND: Randomized trials have established the safety of observation or axillary radiation (AxRT) as an alternative to axillary lymph node dissection (ALND) in patients with limited nodal disease who undergo upfront surgery. Variability remains in axillary management strategies in cN0 patients undergoing mastectomy found to have one to two positive sentinel lymph nodes (SLNs). We examined the impact of intraoperative pathology assessment in axillary management in a national cohort of AMAROS-eligible mastectomy patients. METHODS: The National Cancer Database was used to identify AMAROS-eligible cT1-2N0 breast cancer patients undergoing upfront mastectomy and SLN biopsy (SLNB) and found to have one to two positive SLNs, from 2018 to 2019. We constructed a variable defining intraoperative pathology as 'not performed/not acted on' if ALND was either not performed or performed at a later date than SLNB, or 'performed/acted on' if SLNB and ALND were completed on the same day. Adjusted multivariable analysis examined predictors of treatment with both ALND and AxRT. RESULTS: Overall, 8222 patients with cT1-2N0 disease underwent upfront mastectomy and had one to two positive SLNs. Intraoperative pathology was performed/acted on in 3057 (37.2%) patients. These patients were significantly more likely to have both ALND and AxRT than those without intraoperative pathology (41.0% vs. 4.9%; p < 0.001). On multivariate analysis, the strongest predictor of receiving both ALND and AxRT was use of intraoperative pathology (odds ratio 8.99, 95% confidence interval 7.70-10.5; p < 0.001). CONCLUSIONS: We advocate that consideration should be made for omission of routine intraoperative pathology in mastectomy patients likely to be recommended postmastectomy radiation to minimize axillary overtreatment with both ALND and AxRT in appropriate patients.

Value of Ambulatory Modified Radical Mastectomy.

BACKGROUND: Modified radical mastectomy (MRM) still is largely performed in inpatient settings. This study sought to determine the value (expenditures and complications) of ambulatory MRM. METHODS: Health Care Utilization Project (HCUP) state databases from 2016 were queried for patients who underwent MRM. The study examined rates of 30-day readmission for surgical-site infection (SSI) or hematoma, charges by index care setting, and predictors of 30-day readmission. RESULTS: Overall, 8090 patients underwent MRM: 5113 (63 %) inpatient and 2977 (37 %) ambulatory patients. Compared with the patients who underwent inpatient MRM, those who underwent ambulatory MRM were older (61 vs. 59 years), more often white (66 % vs. 57 %), in the lowest income quartile (28 % vs. 21 %), insured by Medicare (43 % vs. 33 %) and residents in a small metro area (6 % vs. 4 %) (all p < 0.01). Of the 5113 patients treated as inpatients, 126 (2.5 %) were readmitted, whereas 50 (1.7 %) of the ambulatory patients were readmitted (p = 0.02). The adjusted charge for inpatient MRM without readmission was $113,878 (range, $107,355-120,402) compared with $94,463 (range, $86,021-102,907) for ambulatory MRM, and the charge for inpatient MRM requiring readmission was $159,355 (range, $147,142-171,568) compared with $139,940 (range, $125,808-154,073) for ambulatory MRM (all p < 0.01). This difference remained significant after adjustment for hospital length of stay. Adjusted logistic regression showed that the ambulatory setting was protective for readmission (odds ratio, 0.49; 95 % confidence interval, 0.35-0.70; p < 0.01). CONCLUSIONS: The analyses suggest that ambulatory MRM is both safe and less expensive. The findings advocate that MRM, a last holdout of inpatient care within breast surgical oncology, can be transitioned to the ambulatory setting for appropriate patients.

Screening MRI Does Not Increase Cancer Detection or Result in an Earlier Stage at Diagnosis for Patients with High-Risk Breast Lesions: A Propensity Score Analysis.

BACKGROUND: Guidelines recommend consideration of screening MRI for patients with high-risk breast lesions (HRLs), acknowledging limited data for this moderate-risk population. METHODS: This study identified patients with atypical ductal/lobular hyperplasia (ADH/ALH), lobular carcinoma in situ, (LCIS) or both evaluated at our high-risk clinic. Patients were categorized as having received screening mammography (MMG) alone vs. MMG and breast MRI (MMG+MRI). Inverse probability weighting based on propensity scores (PS) representing likelihood of MRI use was applied to Kaplan-Meier and Cox regression analyses to determine cancer detection and biopsy rates by screening group. RESULTS: Among 908 eligible patients, 699 (77%) patients with available follow-up data were analyzed (542 with ADH/ALH and 157 with LCIS). Of the 699 patients, 540 (77%) received MMG alone, and 159 (23%) received MMG + MRI. The median follow-up period was 25 months, during which a median of two MRIs were performed. After PS-weighting, the characteristics of each screening group were well-balanced with respect to age, race, body mass index (BMI), menopausal status, breast density, family history, HRL type, and chemoprevention use. The 4 year breast cancer detection rate was 3.6% with both MMG alone and MMG+MRI (p = 0.89). The breast biopsy rates were significantly higher with MMG+MRI (30.5% vs12.6%; hazard ratio [HR], 2.67; p < 0.001). All breast cancers were clinically node-negative and pathologic stage 0 or 1. Among five cancers in the MMG+MRI group, two were MRI-detected, two were MMG-detected, and one was detected on clinical exam. CONCLUSIONS: Screening MRI did not improve cancer detection, and cancer characteristics were favorable whether screened with MMG alone or MMG + MRI. These findings question the benefit of MRI for patients with HRL, although longer-term follow-up study is needed.

Initiation and tolerance of chemoprevention among women with high-risk breast lesions: the potential of low-dose tamoxifen.

PURPOSE: High-risk lesions (HRLs) of the breast are an indication for chemoprevention, yet uptake is low, largely due to concerns about side effects. In 2019, low-dose (5 mg) tamoxifen was demonstrated to reduce breast cancer risk with improved tolerance. We describe chemoprevention uptake in an academic clinic before and after the introduction of low-dose tamoxifen. METHODS: Females age ≥ 35 with HRLs who established care from April 2017 through January 2020 and eligible for chemoprevention were included. Rates of chemoprevention initiation before and after the introduction of low-dose tamoxifen (pre-2019 vs. post-2019) were compared with chi-squared tests. Logistic regression identified demographic and clinical factors associated with chemoprevention initiation. Kaplan-Meier methods determined the rates of discontinuation. RESULTS: Among 660 eligible females with HRLs, 22.7% initiated chemoprevention. Median time from first visit to chemoprevention initiation was 54 days (interquartile range (IQR): 0-209); 31.0% (46/150) started chemoprevention > 6 months after their initial visit. Chemoprevention uptake was not significantly different pre-2019 vs. post-2019 (21.2% vs. 26.3%, p = 0.16); however, post-2019, low-dose tamoxifen became the most popular option (41.5%, 34/82). On multivariable analyses, age and breast cancer family history were significantly associated with chemoprevention initiation. Discontinuation rates at 1 year were lowest for low-dose tamoxifen (6.7%) vs. tamoxifen 20 mg (15.0%), raloxifene (20.4%), or an aromatase inhibitor (20.0%). CONCLUSION: In this modern cohort, 22.7% of females with HRLs initiated chemoprevention with 31.0% initiating chemoprevention > 6 months after their first visit. Low-dose tamoxifen is now the most popular choice for chemoprevention, with low discontinuation rates at 1 year.

Atypical Lobular Hyperplasia and Classic Lobular Carcinoma In Situ Can Be Safely Managed Without Surgical Excision.

BACKGROUND: Based on modern series demonstrating low upgrade rates for pure lobular neoplasia (LN) diagnosed on core needle biopsy (CNB), our institution no longer recommends routine excision, provided imaging is concordant. This study describes outcomes in patients managed without surgical excision. METHODS: From an institutional database, we identified all patients with a diagnosis of pure atypical lobular hyperplasia and/or classic lobular carcinoma in situ on CNB managed without surgical excision (i.e., conservative management) from 2015 to 2019. The primary outcome of interest was failure of conservative management, defined as development of ipsilateral same-quadrant ductal carcinoma in situ or invasive breast cancer within 2 years of CNB, or need for ipsilateral same-quadrant excisional biopsy. We also evaluated rates of ipsilateral same-quadrant CNB during follow-up. RESULTS: Among 96 pure LN lesions on CNB since 2015, 80 (83%) were managed without surgical excision. Median follow-up was 27 months (IQR: 16-28), with only 2 (2%) patients lost to follow-up. No patients developed an ipsilateral, same-quadrant breast cancer. The 3-year risk of conservative management failure was 6.2% (95% CI 2.3-15.7%). All failures were a result of need for excisional biopsy due to progressive imaging abnormalities at the initial CNB site, with benign final pathology. The 3-year risk of ipsilateral same-quadrant CNB was 9.2% (95% CI 3.8-21.5%). CONCLUSION: Non-surgical management of pure LN is safe, and the likelihood of requiring subsequent surgical excision or repeat CNB during follow-up is low. These data provide reassurance that routine excision of pure LN in the setting of radiologic-pathologic concordance is not required.

Impact of the Histologic Pattern of Residual Tumor After Neoadjuvant Chemotherapy on Recurrence and Survival in Stage I-III Breast Cancer.

BACKGROUND: Additional risk-stratification measures are needed in breast cancer patients with residual disease after neoadjuvant chemotherapy (NAC). We aimed to describe oncologic outcomes in a modern cohort treated with NAC, and evaluate the prognostic value of histologic pattern of residual tumor. PATIENTS AND METHODS: We included patients with stage I-III breast cancer treated with NAC and surgery from 2004 to 2014. Histologic pattern of residual tumor was evaluated by central pathology review when slides were available. Multivariable Cox regression was performed to evaluate factors associated with locoregional recurrence (LRR), recurrence-free survival (RFS), and overall survival (OS). RESULTS: Among 975 patients, median follow-up was 74.0 months and 10-year rates of LRR, RFS, and OS were 9.8%, 67.6% and 74.4%, respectively. Biologic subtype, pathologic node-positive disease, and pathologic complete response (pCR) were associated with outcomes. Among 666 (68.3%) patients with central pathology review, pattern of residual disease was not significantly associated with LRR. However, both scattered residual tumor and no/minimal response relative to a concentric pattern of response were significantly associated with inferior RFS (scattered: hazard ratio 2.0, p = 0.015; no/minimal response: hazard ratio 2.2, p = 0.021) and OS (scattered: hazard ratio 2.2, p = 0.026; no/minimal response: hazard ratio 2.5, p = 0.023). This finding was most prominent in patients with triple-negative breast cancer. CONCLUSIONS: Patients with a scattered relative to concentric pattern of residual tumor after NAC had inferior RFS and OS, nearly as poor as those with no/minimal response. Histologic pattern of residual tumor may represent a novel prognostic measure, particularly in the triple-negative breast cancer population.

Oncotype DX testing in node-positive breast cancer strongly impacts chemotherapy use at a comprehensive cancer center.

PURPOSE: In 2016, we initiated standardized "reflex" Oncotype DX Recurrence Score (RS) testing for patients ≤ 65 years with pT1-2N0-1 HR+/HER2- breast cancer. Here, we examine RS testing patterns, RS distribution, and factors associated with chemotherapy use in patients with pN1 breast cancer. METHODS: Patients with stage I-III HR+/HER2- pN1 breast cancer treated with upfront surgery from February 2016 to March 2019 were identified. Clinical characteristics were compared between patients meeting reflex RS testing criteria, those with RS ordered outside of reflex criteria, and those without RS testing. RS was categorized as low (< 18), intermediate (18-30), and high (≥ 31). Multivariate logistic regression was performed to identify factors associated with adjuvant chemotherapy receipt. We examined 3-year recurrence-free survival (RFS) and overall survival (OS) stratified by chemotherapy use. RESULTS: We identified 347 HR+/HER2- pN1 patients; 272 (78.4%) received RS testing, and 194 (71.3%) met reflex criteria. RS was < 18 in 164 (61.4%) patients, 18-30 in 89 (32.7%) patients, and ≥ 31 in 16 (5.9%) patients. On multivariate analysis, RS < 18 (OR 0.47, 95% CI 0.24-0.92) was associated with lower odds of chemotherapy use, whereas presence of lymphovascular invasion (OR 1.77, 95% CI 1.03-3.07) and lobular subtype (OR 2.40, 95% CI 1.21-4.78) were associated with higher odds. No differences in 3-year RFS (p = 0.97) or OS (p = 0.19) based on chemotherapy receipt were observed. CONCLUSION: Most RS-tested HR+/HER2- pN1 patients at our center had low genomic risk. A low RS independently influenced chemotherapy omission and in RS-tested patients, short-term outcomes were excellent. Our study demonstrates increased use of RS in guiding adjuvant treatment decisions in node-positive disease.

Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer.

Among breast cancer patients treated with neoadjuvant chemotherapy (NAC) who do not experience a pathologic complete response (pCR), the pattern of residual disease in the breast varies. Pre-treatment clinico-pathologic features that predict the pattern of residual tumor are not well established. To investigate this issue, we performed a detailed review of histologic sections of the post-treatment surgical specimens for 665 patients with stage I-III breast cancer treated with NAC followed by surgery from 2004 to 2014 and for whom slides of the post-NAC surgical specimen were available for review. This included 242 (36.4%) patients with hormone receptor (HR)+/HER2- cancers, 216 (32.5%) with HER2+ tumors, and 207 (31.1%) with triple negative breast cancer (TNBC). Slide review was blinded to pre-treatment clinico-pathologic features. pCR was achieved in 7.9%, 37.0%, and 37.7%, of HR+/HER2- cancers, HER2+ cancers, and TNBC respectively (p < 0.001). Among 389 patients with residual invasive cancer in whom the pattern of residual disease could be assessed, 287 (73.8%) had a scattered pattern and 102 (26.2%) had a circumscribed pattern. In both univariate and multivariate analyses, there was a significant association between tumor subtype and pattern of response. Among patients with HR+/HER2- tumors, 89.4% had a scattered pattern and only 10.6% had a circumscribed pattern. In contrast, among those with TNBC 52.8% had a circumscribed pattern and 47.2% had a scattered pattern (p < 0.001). In addition to subtype, histologic grade and tumor size at presentation were also significantly related to the pattern of residual disease in multivariate analysis, with lower grade and larger size each associated with a scattered response pattern (p = 0.002 and p = 0.01, respectively). A better understanding of the relationship between pre-treatment clinico-pathologic features of the tumor and pattern of residual disease may be of value for helping to guide post-chemotherapy surgical management.

Sentinel Node Biopsy Should Not be Routine in Older Patients with ER-Positive HER2-Negative Breast Cancer Who Are Willing and Able to Take Hormone Therapy.

BACKGROUND: The SSO Choosing Wisely campaign recommended selective sentinel lymph node biopsy (SLNB) in clinically node-negative women aged ≥ 70 years with ER+ breast cancer. We sought to assess the association of SLNB positivity, adjuvant treatment, and survival in a population-based cohort. PATIENTS AND METHODS: Women aged ≥ 70 years treated for ER+ HER2- breast cancer between 2010 and 2016 were identified in our prospective provincial database. Overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Kaplan-Meier analysis. Multivariable logistic regression was used to assess the association of SLNB positivity with use of adjuvant treatments and survival outcomes. RESULTS: We identified 2662 patients who met study criteria. SLNB was positive in 25%. Increased use of chemotherapy (ChT), hormone therapy (HT), and radiotherapy (RT) was significantly associated with SLNB positivity. Five-year OS was 86%, and BCSS was 96% with median follow-up of 4.3 years. BCSS was worse with grade 3 disease (HR 4.1, 95% CI 2.1-8.1, p < 0.0001) and better with HT (HR 0.5 95% CI 0.3-0.9, p = 0.01). Patients with a positive SLNB treated without adjuvant therapy had lower BCSS (HR 3.2 95% CI 1.2-8.4, p = 0.017) than those with a negative SLNB, but patients with a positive SLNB treated with any combination of ChT, HT, and/or RT, had similar BCSS to those with a negative SLNB. CONCLUSIONS: BCSS in this population was excellent at 96%, and BCSS was similar with negative and positive SLNB when patients received HT. SLNB can be omitted in elderly patients willing to take HT.

Axillary Management After Neoadjuvant Endocrine Therapy for Hormone Receptor-Positive Breast Cancer.

BACKGROUND: Data to guide axillary management after neoadjuvant endocrine therapy (NET) remain limited. METHODS: We analyzed type of axillary surgery [sentinel lymph node biopsy (SLNB) vs. axillary lymph node dissection (ALND)] and residual nodal disease burden after NET in two cohorts of patients with cT1-4N0-1M0 hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer: Dana-Farber/Brigham and Women's Cancer Center (DFBWCC) cohort (2015-2018) and the National Cancer Data Base (NCDB) cohort (2012-2016). Cox proportional hazard regression was used to determine adjusted 5-year overall survival (OS) by type of axillary surgery. RESULTS: Ninety-four (4.3%) of 2191 HR+/HER2- DFBWCC patients and 4363 (1.5%) of 283,344 NCDB patients were selected for NET. Of those who underwent axillary surgery, 30 (43.5%) in the DFBWCC cohort and 1583 (40.6%) in the NCDB cohort had ALND. Over 90% of cN0 patients in both cohorts had fewer than three positive nodes on final pathology [44 (95.7%) DFBWCC and 2945 (91.3%) NCDB]. In contrast, only 7 (30.4%) DFBWCC patients and 342 (50.7%) NCDB cN1 patients had fewer than three positive nodes. In the DFBWCC patients, there were no locoregional recurrences and four distant recurrences. In the NCDB, 5-year OS did not differ by type of axillary surgery regardless of residual nodal disease burden: 96.6% SLNB versus 97.9% ALND for 0 positive nodes; 84.4% versus 84.4% for one to two positive nodes, and 75.9% versus 77.3% for three or more positive nodes (all p > 0.10). CONCLUSIONS: In cN0 patients selected for NET, > 90% have fewer than three positive nodes at surgery. The lack of a survival difference between SLNB and ALND suggests an opportunity to de-escalate treatment of the axilla in patients with limited residual nodal disease.

Comparison of Breast Cancer Staging Systems After Neoadjuvant Chemotherapy.

BACKGROUND: No consensus exists for optimal staging following neoadjuvant chemotherapy (NAC). We compared the performance of the American Joint Committee on Cancer (AJCC) pathologic prognostic staging system, Residual Cancer Burden (RCB) Index, and the Neo-Bioscore in breast cancer patients after NAC. METHODS: Patients with stage I-III breast cancer who received NAC at Dana-Farber Cancer Institute from 2004 to 2014 were identified. Kaplan-Meier curves were used to estimate disease-free survival (DFS) and overall survival (OS), and model fits were compared by receiver operator characteristic (ROC) curve using the c-statistic and DeLong's test. RESULTS: Overall, 802 patients with a median age of 48 years received NAC. Most patients presented with cT2 (n = 470, 58.6%) and cN1 (n = 422, 52.6%) disease. The subtype was estrogen receptor (ER)- and/or progesterone receptor (PR)-positive/human epidermal growth factor receptor 2 (HER2)-negative in 296 (36.9%) patients, HER2-positive in 261 (32.5%) patients, and triple-negative in 245 (30.5%) patients. Median follow-up was 79.5 months. There were 174 recurrences (30 local, 25 regional, 145 distant), with 676 (76.8%) patients alive at last follow-up. AJCC pathologic prognostic staging and RCB had better discrimination for estimated 7-year DFS and OS compared with the Neo-Bioscore. The ROC c-statistics for DFS model fit were similar for AJCC pathologic prognostic stage (0.72) and RCB (0.71, p = non-significant); both had improved model fit versus the Neo-Bioscore (0.65, p < 0.01). The c-statistics for OS were 0.74, 0.71, and 0.70 for AJCC pathologic prognostic stage, RCB, and Neo-Bioscore, respectively (p = non-significant). CONCLUSIONS: These results validate the ability of these staging systems to stratify survival outcomes in NAC patients, with best discrimination achieved using AJCC pathologic prognostic stage or RCB.

Utility of the 21-Gene Recurrence Score in Node-Positive Breast Cancer.

The 21-gene Recurrence Score (RS) assay has been validated as both a prognostic and predictive tool in node-negative (pN0), estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer. A large body of evidence supports the clinical utility of the RS in the node positive (pN+) population as well. Retrospective analyses of archived tissue from multiple clinical trials have found the RS to be prognostic in both endocrine therapy (ET)-treated and chemotherapy-treated patient with pN+ disease. Distribution of RS results in pN+ patients have also been consistent with those of pN0 populations. Data from the SWOG 8814 trial and large population-based registries further support the prognostic and potential predictive value of the RS. Specifically, patients with 1 to 3 positive nodes and RS less than 18 derived negligible benefit from adjuvant chemotherapy in these studies. In the prospective West German Study Group PlanB and ADAPT trials, pN+ patients with RS less than 11 and RS 25 or less, respectively, who were treated with ET alone experienced excellent outcomes. Finally, 5-year results of the RxPONDER clinical trial randomizing patients with 1 to 3 positive nodes and RS 25 or less to ET alone vs ET plus chemotherapy confirmed an absence of chemotherapy benefit in postmenopausal patients. Clinical practice guidelines support use of the RS in the pN+, ER+/HER2- population, and many institutions have adopted the RS to guide clinical decisionmaking, resulting in a net reduction of adjuvant chemotherapy use. This review highlights the existing data supporting the prognostic and predictive ability of the RS in pN+ disease, current practice patterns related to RS use in this population, and emerging applications.

Breast Biopsy During Post-treatment Surveillance of Screen-Detected Breast Cancer Patients Yields High Rates of Benign Findings.

BACKGROUND: The incidence of breast biopsy following treatment for breast cancer is not well-characterized. We sought to determine the frequency and outcomes of breast biopsy and the need for subsequent surgery in patients treated with breast-conserving surgery (BCS). METHODS: Using a prospective database, we identified patients in Alberta, Canada, treated with BCS for screen-detected breast cancer or ductal carcinoma in situ (DCIS) from 2010 to 2014. Post-treatment breast procedures were identified from physician claims data. Multivariable analysis was performed to identify factors associated with biopsy. RESULTS: We included 2065 patients with a median of 6.4 years of follow-up; most had DCIS (n = 426, 20.6%) or stage I disease (n = 1385, 67.1%). Post-treatment core biopsy was performed in 389 (18.8%, 95% confidence interval [CI] 17.2-20.6%) patients, and excisional biopsy was performed in 19 (0.9%, 95% CI 0.6-1.4%) patients. The per-patient benign-to-malignant biopsy ratio was 3.2 to 1, and the overall malignancy rate was 6.1% (95% CI 5.1-7.2%). Younger age, proximity to a cancer center, positive margins, and the use of magnetic resonance imaging were associated with biopsy (p < 0.05). Additional surgery was performed in 150 (7.3%, 95% CI 6.2-8.5%) patients; 93 (4.5%, 95% CI 3.6-5.4%) patients underwent mastectomy. Surgery was performed for local recurrence/ipsilateral cancer in 62 (3.0%) patients, contralateral breast cancer in 60 (2.9%) patients, bilateral breast cancer in 3 (0.1%) patients, and benign indications/prophylaxis in 25 (1.2%) patients. CONCLUSIONS: One in five patients required breast biopsy during post-treatment surveillance following BCS and most revealed benign findings. Rates of additional surgery, especially subsequent mastectomy due to ipsilateral or contralateral malignancy, were low. Patients can be reassured of these findings during pre-treatment counseling and post-treatment surveillance.

Node-Positive Patients Treated with Neoadjuvant Chemotherapy Can Be Spared Axillary Lymph Node Dissection with Wireless Non-Radioactive Localizers.

BACKGROUND: Targeted axillary dissection (TAD) involves sentinel lymph node biopsy (SLNB) and excision of a biopsy-proven node marked by a clip. This study evaluates the feasibility of non-radioactive wireless localizers for targeted excision of clipped axillary lymph nodes. METHODS: We identified biopsy-proven, node-positive breast cancer patients treated with neoadjuvant therapy (NAT) and TAD from 2016 to 2020, and included those with a clipped node localized using SAVI SCOUT, Magseed, or RFID Tag. Primary outcome measures were (1) successful localization (ultrasound or mammographic-guided placement < 10 mm from target), and (2) retrieval of the clipped node during TAD, documented by specimen radiography or gross visualization. Secondary outcomes included rates of completion axillary lymph node dissection (cALND) and complications. RESULTS: Overall, 57 patients were included; 1 (1.8%) patient had no clip visible at the time of localization, and no radiographic confirmation of clip placement at the time of biopsy, and was therefore excluded. In the remaining 56 patients, localization was successful in 53 (94.6%) patients and the clipped node was retrieved during TAD in 51 (91.1%) patients. Twenty-three of 27 (85.2%) ypN0 patients were spared cALND; 3 (11.1%) patients had cALND for failed clipped node retrieval during TAD, and 1 (3.7%) for false-positive frozen section. In patients with TAD alone, the rates of axillary seroma and infection were 20.0% and 8.6%, respectively. CONCLUSIONS: Wireless non-radioactive localizers are feasible for axillary localization after NAT, with high success rates of retrieving clipped nodes. The lack of signal decay is an advantage of these devices, allowing flexibility in timing of placement.

Baseline Screening MRI Uptake and Findings in Women with ≥ 20% Lifetime Risk of Breast Cancer.

BACKGROUND: The American Cancer Society recommends screening magnetic resonance imaging (MRI) for patients with a ≥ 20% lifetime breast cancer risk. This study assesses the outcomes of baseline MRI screens in women from a high-risk breast clinic (HRBC). METHODS: We retrospectively reviewed patients from our institution's HRBC, excluding those with prior breast cancer and predisposing genetic mutations. Screening MRI was recommended for a lifetime risk of ≥ 20% using the Tyrer-Cuzick model. We determined baseline MRI results, biopsy rates, and frequency of MRI-detected high-risk lesions (HRLs) and breast cancers. RESULTS: Overall, 319 women attended our HRBC; median age was 48 years and 4.7% had prior atypia/lobular carcinoma in situ. Screening MRI was recommended for 282 patients, of whom 196 (69.5%) completed a baseline screen. A Breast Imaging-Reporting and Data System (BIRADS) 3 or 4 finding occurred in 19.6% of patients; 23 (12.3%) required 6-month follow-up MRI, 16 (8.6%) underwent core biopsy, and 4 (2.1%) underwent excisional biopsy after initial core. An additional 7 (3.7%) patients had a non-breast incidental finding. An HRL was identified in 2 (1.1%) patients (atypical ductal and lobular hyperplasia, respectively), and 2 (1.1%) were diagnosed with T1N0 breast cancers. CONCLUSIONS: In the setting of an HRBC, 70% of women with a ≥ 20% lifetime risk of breast cancer pursued screening MRI when recommended. On baseline screen, the rate of MRI-detected breast cancer was low (1%); however, malignancies were mammographically occult and identified at an early stage. Despite a low cancer rate, nearly one in four women required additional diagnostic investigation. Prescreening counselling should include a discussion of this possibility, and longer-term follow-up of screening MRI is needed in this high-risk population.

Improving Wait Times and Patient Experience Through Implementation of a Provincial Expedited Diagnostic Pathway for BI-RADS 5 Breast Lesions.

BACKGROUND: Long diagnostic intervals following abnormal breast imaging (DI) cause patient anxiety and possibly poorer prognosis. This study evaluates the effect of a provincial diagnostic pathway for BI-RADS 5 lesions on wait times and the patient-reported experience (PRE). METHODS: With multidisciplinary input, we developed a pathway for BI-RADS 5 lesions featuring expedited biopsy, early surgical referral, and nurse (RN) navigator support. Key diagnostic intervals were captured prospectively and compared with a prepathway control cohort. PRE data were obtained from a voluntary survey. RESULTS: 1205 patients were managed on the BI-RADS 5 pathway with 797 primary care physicians, 57 imaging centers, and 2 regional breast programs participating. Median duration from DI to biopsy was 6 days, from biopsy to pathology report was 5 days, DI to surgical referral was 6 days, and DI to surgical consult was 21 days. Compared with 128 prepathway controls, median intervals from DI to surgical referral and consult were significantly improved (15 vs. 6 days, 26 vs. 21 days, p < 0.001). Amongst 294 women who completed the survey, 92% experienced ≥ 1 anxiety complaint during assessment; prompt surgical consultation and multiple features of RN support reduced anxiety, and wait time satisfaction was high (70%). Patient preferences varied for receiving biopsy results from a surgeon (57%) vs. another provider (43%). CONCLUSIONS: A diagnostic pathway for BI-RADS 5 lesions reduced wait times and improved the patient experience through prompt surgical referral and RN navigator support. Differing preferences for receiving biopsy results emerged, and future iterations should incorporate individualized patient wishes.

Same-Day Surgery for Mastectomy Patients in Alberta: A Perioperative Care Pathway and Quality Improvement Initiative.

BACKGROUND: Same-day surgery (SDS) following mastectomy is safe and well accepted. Overnight admission in patients fit for discharge is an inefficient use of health resources. In response to a national review highlighting SDS following mastectomy at 1.4% in Alberta, a perioperative pathway was conceived. METHODS: The pathway was implemented across Alberta at 13 hospitals beginning in 2016. A steering committee was assembled, and clinical and administrative leads at each site were identified. Opportunities along the patient care experience whereby action could be taken to promote uptake of SDS were identified. Provincially branded support materials including presentations, order sets, and standard operating procedures were developed. Nurse educators provided in-service teaching such as standardized drain care and discharge teaching. Educational booklets, group classes, and online resources were developed for patients and families. An audit of SDS rates, unscheduled return to the emergency department (ED), and readmission rates was reported to teams quarterly, allowing for iterative modifications. Patient-reported experience measures (PREMs) were collected. RESULTS: SDS following mastectomy increased from 1.7 to 47.8%, releasing an estimated 831 bed days per year. No differences in unexpected return to the ED or readmission to hospital existed between SDS patients and those admitted overnight. A total of 102 patients completed the PREM survey, of whom 90% felt "excellent or good" with the plan to go home, how to care for themselves once home, and who to contact should issues arise. CONCLUSIONS: Implementation of a provincial perioperative pathway improved uptake of SDS following mastectomy and demonstrated favorable PREMs.