Breast lymphedema following breast-conserving treatment for breast cancer: current status and future directions.

PURPOSE: To examine the current evidence on breast lymphedema (BL) diagnosis and treatment after breast-conserving surgery, identify gaps in the literature, and propose future research directions. METHODS: A comprehensive literature review was conducted using Ovid, PubMed, and Cochrane, including studies published between 2000 and 2023. References were reviewed manually for eligible studies. Inclusion criteria were as follows: patients who underwent breast conserving treatment (surgery ± radiation) for breast cancer, goals of the paper included analyzing or reviewing BL measurement with ultrasound or tissue dielectric constant, or BL treatment. Twenty-seven manuscripts were included in the review. RESULTS: There is variation in incidence, time course, and risk factors for BL. Risk factors for BL included breast size, primary and axillary surgery extent, radiation, and chemotherapy but require further investigation. Diagnostic methods for BL currently rely on patient report and lack standardized criteria. Tissue dielectric constant (TDC) and ultrasound (US) emerged as promising ambulatory BL assessment tools; however, diagnostic thresholds and validation studies with ICG lymphography are needed to establish clinical utility. The evidence base for treatment of BL is weak, lacking high-quality studies. CONCLUSION: The natural history of BL is not well defined. TDC and US show promise as ambulatory assessment tools for BL; however, further validation with lymphatic imaging is required. BL treatment is not established in the literature. Longitudinal, prospective studies including pre-radiation measurements and validating with lymphatic imaging are required. These data will inform screening, diagnostic criteria, and evidence-based treatment parameters for patients with BL after breast-conserving surgery and radiation.

A multi-institutional prediction model to estimate the risk of recurrence and mortality after mastectomy for T1-2N1 breast cancer.

BACKGROUND: Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial. METHODS: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1-2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM). RESULTS: A total of 3532 patients were included for analysis with a median follow-up time among survivors of 6.8 years (interquartile range [IQR], 4.5-9.5 years). The 2154 (61%) patients who received PMRT had significantly more adverse risk factors than those patients not receiving PMRT: younger age, larger tumors, more positive lymph nodes, lymphovascular invasion, extracapsular extension, and positive margins (p < .05 for all). On competing risk regression analysis, receipt of PMRT was significantly associated with a decreased risk of LRR (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.14-0.31; p < .001) and OR (HR, 0.76; 95% CI, 0.62-0.94; p = .011). Model performance metrics for each end point showed good discrimination and calibration. An online prediction model to estimate predicted risks for each outcome based on individual patient and tumor characteristics was created from the model. CONCLUSIONS: In a large multi-institutional cohort of patients, PMRT for T1-2N1 breast cancer was associated with a significant reduction in locoregional and overall recurrence after accounting for known prognostic factors. An online calculator was developed to aid in personalized decision-making regarding PMRT in this population.

Diagnostic Criteria for Breast Cancer-Related Lymphedema of the Upper Extremity: The Need for Universal Agreement.

With advances in breast cancer treatments and resultant increased survival rates, emphasis has been placed on post-treatment complications such as breast cancer-related lymphedema (BCRL), a chronic, negative sequela of breast cancer treatment. Accurate BCRL diagnosis necessitates longitudinal screening beginning at preoperative baseline. Prospective screening programs incorporating symptoms, objective measurements and clinical examination allow for early detection, early intervention, and improved BCRL prognosis. Currently, varied diagnostic criteria for BCRL exist, and this lack of consensus leads to variation in diagnostic and screening practices across institutions. This review outlines current diagnostic tools, including subjective and objective measurement methods and clinical examination. The merits of different criteria are evaluated and recommendations are made regarding measurement tools and diagnostic criteria for BCRL. Ultimately, the BCRL diagnostic process should be universalized and combine objective measurements, clinical evaluation, and symptoms assessment, and adhere to the best practices of the measurement tools used.

Weight loss does not decrease risk of breast cancer-related arm lymphedema.

BACKGROUND: The goal of this study was to determine the relationship between postoperative weight change and breast cancer-related lymphedema (BCRL). METHODS: In this cohort study, 1161 women underwent unilateral breast surgery for breast cancer from 2005 to 2020 and were prospectively screened for BCRL. Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6 to 12 months. Mean follow-up from preoperative baseline was 49.1 months. The main outcome was BCRL, defined as a relative volume change of the ipsilateral arm of ≥10% at least 3 months after surgery. RESULTS: A total of 92 patients (7.9%) developed BCRL. Net weight loss versus net weight gain from baseline to last follow-up was not protective against developing BCRL (hazard ratio, 1.38; 95% confidence interval, 0.89-2.13; P = .152). CONCLUSIONS: Although weight loss may be recommended as part of an individualized lifestyle management program for overall health, weight loss alone may not decrease the risk of developing BCRL.

Locally Recurrent Secretory Carcinoma of the Breast with NTRK3 Gene Fusion.

Enhanced understanding of the molecular events underlying oncogenesis has led to the development of "tumor-agnostic" treatment strategies, which aim to target a tumor's genomic profile regardless of its anatomic site of origin. A classic example is the translocation resulting in an ETV6-NTRK3 gene fusion, a characteristic driver of a histologically diverse array of cancers. The chimeric ETV6-NTRK3 fusion protein elicits constitutive activation of the tropomyosin receptor kinase (TRK) C protein, leading to increased cell survival, growth, and proliferation. Two TRK inhibitors, larotrectinib and entrectinib, are currently approved for use in the metastatic setting for the treatment of advanced solid tumors harboring NTRK fusions. Here we report a rare case of recurrent secretory carcinoma of the breast (SCB) with NTRK3 gene fusion. Whereas most cases of SCB represent slow-growing tumors with favorable outcomes, the case detailed here is the first to the authors' knowledge of recurrence within 1 year of surgery. We review the molecular findings and potential clinical significance. KEY POINTS: The translocation resulting in the ETV6-NTRK3 gene fusion is a known oncogenic driver characteristic of secretory carcinoma of the breast (SCB). Whereas most cases of SCB represent slow-growing tumors with favorable outcomes, the case here with ETV6-NTRK3 gene fusion had local recurrence within 1 year of surgery. Two tropomyosin receptor kinase (TRK) inhibitors, larotrectinib and entrectinib, are approved to treat NTRK fusion-positive tumors, demonstrating sustained high overall response rates in the metastatic setting. Approval of TRK inhibitors necessitates optimization of NTRK fusion detection assays, including detection with liquid biopsies.

Subclinical Lymphedema After Treatment for Breast Cancer: Risk of Progression and Considerations for Early Intervention.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a devastating complication of breast cancer (BC) treatment. The authors hypothesized that identifying subclinical lymphedema (SCL) presents an opportunity to prevent BCRL development. They aimed to assess rates of SCL progression (relative volume change [RVC], 5-10%) to BCRL (RVC, ≥10%) in women undergoing axillary surgery for BC via axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB). METHODS: Patients treated for BC were prospectively screened at preoperative baseline and throughout the follow-up period using the perometer. The cohort was stratified according to nodal surgery (ALND or SLNB) to analyze rates of progression to BCRL. RESULTS: The study cohort included 1790 patients. Of the 1359 patients who underwent SLNB, 331 (24.4%) experienced SCL, with 38 (11.5%) of these patients progressing to BCRL. Of the 431 patients who underwent ALND, 171 (39.7%) experienced SCL, with 67 (39.2%) of these patients progressing to BCRL. Relative to the patients without SCL, those more likely to experience BCRL were the ALND patients with early SCL (< 3 months postoperatively; hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.58-4.27; p = 0.0002) or late SCL (≥3 months postoperatively; HR, 3.14; 95% CI, 1.95-5.05; p < 0.0001) and the SLNB patients with early SCL (HR, 6.75; 95% CI, 3.8-11.98; p < 0.0001 or late SCL (HR, 3.02; 95% CI, 1.65-5.50; p = 0.0003). CONCLUSION: The study suggests that patients with SCL after axillary nodal surgery for BC are more likely to progress to BCRL than those who do not experience SCL. This presents a tremendous opportunity for early intervention to prevent BCRL and improve the quality of life for women treated for BC.

Standardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers.

Practice changing standardization of lower extremity lymphedema quantitative measurements with integrated patient reported outcomes will likely refine and redefine the optimal risk-reduction strategies to diminish the devastating limb-related dysfunction and morbidity associated with treatment of gynecologic cancers. The National Cancer Institute (NCI), Division of Cancer Prevention brought together a diverse group of cancer treatment, therapy and patient reported outcomes experts to discuss the current state-of-the-science in lymphedema evaluation with the potential goal of incorporating new strategies for optimal evaluation of lymphedema in future developing gynecologic clinical trials.

Lymphoedema screening: setting the standard.

Existing literature which is changing practice should be scrutinised, in the interest of all women at risk for lymphoedema after breast cancer (BC). Bundred et al.'s prospective, multicentre trial of 1100 women made several solid findings, and novel screening recommendations presented may assist in incorporating lymphoedema screening into standard of care.

Optimal breast reconstruction type for patients treated with neoadjuvant chemotherapy, mastectomy followed by radiation therapy.

PURPOSE: To explore the optimal type of breast reconstruction and the time interval to postmastectomy radiotherapy (PMRT) associated with lower complications in breast cancer patients receiving neoadjuvant chemotherapy. METHODS: We reviewed the medical records of 300 patients who received neoadjuvant chemotherapy, mastectomy with breast reconstruction and PMRT at our institution from 2000 to 2017. Reconstruction types included autologous flaps (AR), single-stage-direct-to-implant and two-stages expander/implant (TE/I). The primary endpoint was the rate of reconstruction complications including infection, skin and fat necrosis. Subgroup analysis compared rates of capsular contracture, implant rupture, implant exposure and overall implant failure in single-stage-direct-to-implant to TE/I. The secondary endpoint was identifying the time interval between surgery with immediate implant-based reconstruction and PMRT associated with lower probability of implant failure. Logistic regression models, Kaplan-Meier estimates and Polynomial regression were used to assess endpoints. RESULTS: The median follow-up was 43.5 months. 29.3%, 28.3% and 42.4% of the cohort had AR, TE/I and single-stage-direct-to-implant D, respectively. The 5-year cumulative incidence rate of complications was 14.0%, 29.7% and 19.4% for AR, TE/I and single-stage-direct-to-implant, respectively (Log rank p = 0.02). Multivariate analysis showed significant association between TE/I and higher risk of infection (OR 8.1, p = 0.009) compared to AR, while single-stage-direct-to-implant and AR were comparable (OR 3.2, p = 0.2). On subgroup analysis, TE/I was significantly associated with higher rates of implant failure. The mean wait time to deliver PMRT after immediate reconstruction with no adjuvant chemotherapy was 8.4 and 10.7 weeks in single-stage-direct-to-implant and TE/I, respectively (p < 0.005). Delivering PMRT after 8 weeks of surgery yielded 10% probability of reconstruction failure in single-stage-direct-to-implant versus 40% in TE/I. CONCLUSION: In comparison to two stages reconstruction, single-stage-direct-to-implant following neoadjuvant chemotherapy has lower complications and offers timely delivery of PMRT.

Patients who report cording after breast cancer surgery are at higher risk of lymphedema: Results from a large prospective screening cohort.

OBJECTIVES: To identify the association between cording and breast cancer-related lymphedema (BCRL); describe time course, location, symptoms and functional impairments. METHODS: A total of 1181 patients were prospectively screened for BCRL after breast cancer (BC) surgery, including patient-reported outcome measures (4193) and perometric arm volume measurements (BCRL defined as relative or weight-adjusted volume change [RVC or WAC] ≥10% ≥3 months postoperatively). RESULTS: A total of 374/1181 patients (31.7%) reported cording first a median of 4.5 months postoperatively, and were more likely to: have body mass index less than 30 kg/m2 ; be less than 55 years of age; have had mastectomy, axillary lymph node dissection, regional lymph node radiation, neoadjuvant chemotherapy (all P < .001), or RVC/WAC ≥10% (P = .002). Patients who reported cording had 2.4 times the odds of developing BCRL compared to those who did not (odds ratio = 2.40; 95% confidence interval = 1.40-4.11; P = .002), and most frequently reported these symptoms: tenderness (61.2%), aching (60.7%), and firmness/tightness (59.8%). On multivariable analysis, cording was significantly correlated with functional difficulty for 17 actions. CONCLUSIONS: Patients frequently present with cording, potentially months after BC surgery. Risk factors for and symptoms of cording are identified, and treatment is recommended. Patients reporting cording are at higher risk of BCRL, therefore, cording should be incorporated into BCRL risk stratification.

Incidence of peripheral edema in patients receiving PI3K/mTOR/CDK4/6 inhibitors for metastatic breast cancer.

PURPOSE: This study evaluated development of edema in patients receiving PI3K/mTOR/CDK4/6 targeted therapy for metastatic breast cancer (MBC). METHODS: We reviewed medical records of 160 patients receiving targeted therapy with PI3K/mTOR/CDK4/6 inhibitors to treat MBC (n = 160; 185 treatment occurrences). Clinicopathologic data, treatment details, and edema incidence were recorded. RESULTS: Edema incidence was 43.1% (69/160) overall and 25.6% (41/160) in the upper extremity ipsilateral to the treated breast. In 185 therapy regimens administered, 6.8% of patients on a PI3K inhibitor, 8.8% of patients on an mTOR inhibitor, and 9.2% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting upper extremity edema. Further, 9.1% of patients on a PI3K inhibitor, 18.8% of patients on an mTOR inhibitor, and 10.5% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting edema elsewhere in the body. Multivariate logistic regression showed that, beyond the established breast cancer-related lymphedema (BCRL) risk factors [axillary lymph node dissection (Odds Ratio (OR) 2.69, p = 0.020), regional lymph node irradiation (OR 6.47, p < 0.001), and body-mass index ≥ 30 kg/m2 (OR 3.46, p = 0.006)], a relative decrease in serum albumin after 3 months of treatment increased risk of developing edema (OR 2.07, p = 0.062). Neither duration nor type of therapy were significant risk factors for edema. CONCLUSION: PI3K/mTOR/CDK4/6 inhibitors may influence the development of edema, which may cause or exacerbate progression of BCRL in patients with MBC. The varied incidence of edema between therapeutic regimens warrants vigilant monitoring of patients treated with these therapies, especially those at high risk of developing BCRL.

Evaluation of radiation-induced cardiac toxicity in breast cancer patients treated with Trastuzumab-based chemotherapy.

PURPOSE: Patients with Her2-positive breast cancer treated with trastuzumab have higher rates of cardiotoxicity (CT). Left-breast radiation might increase the risk for CT from cardiac exposure to radiation. The goal of our study is to evaluate the contribution of radiotherapy (RT) in the development of CT in breast cancer patients receiving trastuzumab. METHODS: Two hundred and two patients were treated with RT and trastuzumab from 2000 to 2014. The RT plans for left-side disease were recalled from archives. The heart, each chamber, and left anterior descending artery (LAD) were independently contoured. New dose-volume histograms (DVH) were generated. Their serial left-ventricular ejection fractions (LVEF) were studied. CT for left and right side were compared using Fisher's exact test. The DVH data were correlated with the predefined cardiac events using actuarial Cox regression analysis. RESULTS: Compared to the right sided, the left-side cases showed statistically significant development of arrhythmia (14.2%) versus (< 1%) (p < 0.001). Cardiac ischemia was found in 10 patients in left and one patient in right side (p = 0.011). The equivalent uniform dose (EUD) to the left ventricle (LV), right ventricle (RV), and LAD was significantly associated with decrease in LVEF by > 10% (p = 0.037, p = 0.023 and p = 0.049, respectively). CONCLUSIONS: Among patients treated for left-sided lesions, there were no significant differences in EF decline. However, there was a higher rate of ischemia and arrhythmia compared to those with right-sided disease. The EUD index of LV, RV, and LAD could be considered as a parameter to describe the risk of radiation-induced CT.

Tattoo free setup for partial breast irradiation: A feasibility study.

PURPOSE: Patients undergoing external beam accelerated partial breast irradiation (APBI) receive permanent tattoos to aid with daily setup alignment and verification. With the advent of three-dimensional (3D) body surface imaging and two-dimensional (2D) x-ray imaging-based matching to surgical clips, tattoos may not be necessary to ensure setup accuracy. We compared the accuracy of conventional tattoo-based setups to a patient setup without tattoos. MATERIALS/METHODS: Twenty consecutive patients receiving APBI at our institution from July 10, 2017 to February 13, 2018 were identified. All patients received tattoos per standard of care. Ten patients underwent setup using tattoos for initial positioning followed by surface imaging and 2D matching of surgical clips. The other ten patients underwent positioning using surface imaging followed by 2D matching without reference to tattoos. Overall setup time and orthogonal x-ray-based shifts after surface imaging per fraction were recorded. Shift data were used to calculate systematic and random error. RESULTS: Among ten patients in the "no tattoo" group, the average setup time per fraction was 6.83 min vs 8.03 min in the tattoo cohort (P < 0.01). Mean 3D vector shifts for patients in the "no tattoo" group were 4.6 vs 5.9 mm in the "tattoo" cohort (P = NS). Mean systematic errors in the "no tattoo" group were: 1.2 mm (1.5 mm SD) superior/inferior, 0.5 mm (1.6 mm SD) right/left, and 2.3 mm (1.9 mm SD) anterior/posterior directions. Mean systematic errors in the "tattoo" group were: 0.8 mm (2.2 mm SD) superior/inferior, 0.3 mm (2.5 mm SD) right/left, and 1.4 mm (4.4 mm SD) anterior/posterior directions. The random errors in the "no tattoo" group ranged from 0.6 to 0.7 mm vs 1.2 to 1.7 mm in the "tattoo" group. CONCLUSIONS: Using both surface imaging and 2D matching to surgical clips provides excellent accuracy in APBI patient alignment and setup verification with reduced setup time relative to the tattoo cohort. Skin-based tattoos may no longer be warranted for patients receiving external beam APBI.

Machine learning to parse breast pathology reports in Chinese.

INTRODUCTION: Large structured databases of pathology findings are valuable in deriving new clinical insights. However, they are labor intensive to create and generally require manual annotation. There has been some work in the bioinformatics community to support automating this work via machine learning in English. Our contribution is to provide an automated approach to construct such structured databases in Chinese, and to set the stage for extraction from other languages. METHODS: We collected 2104 de-identified Chinese benign and malignant breast pathology reports from Hunan Cancer Hospital. Physicians with native Chinese proficiency reviewed the reports and annotated a variety of binary and numerical pathologic entities. After excluding 78 cases with a bilateral lesion in the same report, 1216 cases were used as a training set for the algorithm, which was then refined by 405 development cases. The Natural language processing algorithm was tested by using the remaining 405 cases to evaluate the machine learning outcome. The model was used to extract 13 binary entities and 8 numerical entities. RESULTS: When compared to physicians with native Chinese proficiency, the model showed a per-entity accuracy from 91 to 100% for all common diagnoses on the test set. The overall accuracy of binary entities was 98% and of numerical entities was 95%. In a per-report evaluation for binary entities with more than 100 training cases, 85% of all the testing reports were completely correct and 11% had an error in 1 out of 22 entities. CONCLUSION: We have demonstrated that Chinese breast pathology reports can be automatically parsed into structured data using standard machine learning approaches. The results of our study demonstrate that techniques effective in parsing English reports can be scaled to other languages.

Perometry versus simulated circumferential tape measurement for the detection of breast cancer-related lymphedema.

PURPOSE: Despite increasing emphasis on screening and early intervention for breast cancer-related lymphedema (BCRL), there is marked heterogeneity in diagnostic methodology, including for volumetric measures. This retrospective study compared two volumetric modalities, perometry and simulated circumferential tape measurement (anatomic- and interval-based), for BCRL detection. METHODS: Between 2005 and 2017, 287 female patients with unilateral breast cancer were prospectively screened for BCRL by perometry and the relative volume change (RVC) formula. Circumferential measurement was performed by sampling at five anatomic landmark-based points or 4-cm intervals from pairs of perometer arm diameter measurements. Volumetric conversion was by a frustum model. The Bland-Altman method was used to compare segmental volume differences. Confusion matrix analysis was performed for each circumferential measurement technique against perometry. RESULTS: Median follow-up was 34.7 months over 4 postoperative visits. There was no difference in total arm volume comparing any of the circumferential measurement techniques to perometry. Landmark-based methods significantly underestimated upper arm volume (mean difference - 207 mL [- 336, - 78 mL]) and overestimated forearm volume (mean difference + 170 mL [+ 105, + 237 mL]). Landmark-based methods had greater sensitivity and specificity compared to 4-cm interval methods for detection of both RVC ≥ 10 and 5-10%. Landmark-based methods were comparable to perometry for detection of RVC ≥ 10%, but sensitivity was only 63.2-66.7% for RVC 5-10%. CONCLUSIONS: This hypothesis-generating study suggested the superiority of anatomic landmark-based circumferential tape measurement compared to interval-based methods, while generating questions about the underestimation of upper arm volume and overestimation of forearm volume of circumferential tape measurement compared to perometry.

Predictors of surveillance mammography outcomes in women with a personal history of breast cancer.

PURPOSE: To identify predictors of poor mammography surveillance outcomes based on clinico-pathologic features. METHODS: This study was HIPAA compliant and IRB approved. We performed an electronic medical record review for a cohort of women with American Joint Committee on Cancer (AJCC) Stage I or II invasive breast cancer treated with breast conservation therapy who developed subsequent in-breast treatment recurrence (IBTR) or contralateral breast cancer (CBC). Poor surveillance outcome was defined as second breast cancer not detected by surveillance mammography, including interval cancers (diagnosed within 365 days of surveillance mammogram with negative results) and clinically detected cancers (diagnosed without a surveillance mammogram in the preceding 365 days). Univariate and multivariate logistic regression were performed to identify predictors of poor mammography surveillance outcome, including patient and primary tumor characteristics, breast density, mode of primary tumor detection, and time to second cancer diagnosis. RESULTS: 164 women met inclusion criteria (65 with IBTR, 99 with CBC); 124 had screen-detected second cancers. On univariate analysis, poor surveillance outcome (n = 40) was associated with age at primary cancer diagnosis < 50 years (p < 0.0001), AJCC stage II primary cancers (p = 0.007), and heterogeneously or extremely dense breasts (p = 0.04). On multivariate analysis, age < 50 years at primary breast cancer diagnosis remained a significant predictor of poor surveillance outcome (p = 0.001). CONCLUSION: Women younger than age 50 at primary breast cancer diagnosis are at risk of poor surveillance mammography outcomes, and may be appropriate candidates for more intensive clinical and imaging surveillance.

Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer.

PURPOSE: Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH. METHODS: We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis were used for statistical analysis. RESULTS: In this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation. CONCLUSIONS: Pertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.

Predictors of Disruptions in Breast Cancer Care for Individuals with Schizophrenia.

BACKGROUND: Patients with schizophrenia experience markedly increased breast cancer mortality, yet reasons for this disparity are poorly understood. We sought to characterize disruptions in breast cancer care for patients with schizophrenia and identify modifiable predictors of those disruptions. MATERIALS AND METHODS: We performed a medical record review of 95 patients with schizophrenia and breast cancer treated at an academic cancer center between 1993 and 2015. We defined cancer care disruptions as processes that interfere with guideline-concordant cancer care, including delays to diagnosis or treatment, deviations from stage-appropriate treatment, and interruptions in treatment. We hypothesized that lack of psychiatric treatment at cancer diagnosis would be associated with care disruptions. RESULTS: Half of patients with schizophrenia experienced at least one breast cancer care disruption. Deviations in stage-appropriate treatment were associated with breast cancer recurrence at 5 years (p = .045). Patients without a documented psychiatrist experienced more delays (p = .016), without documented antipsychotic medication experienced more deviations (p = .007), and with psychiatric hospitalizations after cancer diagnosis experienced more interruptions (p < .0001). Independent of stage, age, and documented primary care physician, lack of documented antipsychotic medication (odds ratio [OR] = 4.97, 95% confidence interval [CI] = 1.90, 12.98) and psychiatric care (OR = 4.56, 95% CI = 1.37, 15.15) predicted cancer care disruptions. CONCLUSION: Disruptions in breast cancer care are common for patients with schizophrenia and are associated with adverse outcomes, including cancer recurrence. Access to psychiatric treatment at cancer diagnosis may protect against critical disruptions in cancer care for this underserved population. IMPLICATIONS FOR PRACTICE: Disruptions in breast cancer care are common for patients with schizophrenia, yet access to mental health treatment is rarely integrated into cancer care. When oncologists documented a treating psychiatrist and antipsychotic medication, patients had fewer disruptions in breast cancer care after adjusting for age, cancer stage, and access to primary care. Addressing psychiatric comorbidity at breast cancer diagnosis may increase the likelihood that patients with schizophrenia receive timely, stage-appropriate cancer treatment. Comanagement of schizophrenia and breast cancer at cancer diagnosis may be one key strategy to decrease inequities in cancer treatment and improve cancer survival in this underserved population.

Breast-cancer subtype, age, and lymph node status as predictors of local recurrence following breast-conserving therapy.

PURPOSE/OBJECTIVES: Advances in breast-conserving therapy (BCT) have yielded local control rates comparable or superior to those of mastectomy. In this study, we sought to identify contemporary risk factors associated with local recurrence (LR) following BCT. METHODS: We analyzed a multi-institutional cohort of 2233 consecutive breast-cancer patients who underwent BCT between 1998 and 2007. Patients were stratified by age, biologic subtype (as approximated by receptor status and tumor grade), and nodal status. Patients who received HER2/neu-directed therapy were excluded due to variations in practice over the study period. The association of clinicopathologic features with LR was evaluated using Cox proportional hazards regression models. RESULTS: With a median follow-up of 106 months, 69 LRs (3 %) were observed. On univariate analysis, LR was associated with non-luminal-A subtype (hazard ratio [HR] for luminal-B = 3.01, HER2 = 6.29, triple-negative [TNBC] = 4.72; p < 0.001 each), younger age (HR of oldest vs. youngest quartile = 0.43; p = 0.005), regional nodal involvement (HR for 4-9 involved nodes = 3.04; >9 nodes = 5.82; p < 0.01 for each), positive margins (HR 2.43; p = 0.005), and high grade (HR 5.37; p < 0.001). Multivariate Cox regression demonstrated that non-luminal-A subtypes (HR for luminal-B = 2.64, HER2 = 5.42, TNBC = 4.32; p < 0.001 for each), younger age (HR for age >50 = 0.56; p = 0.01), and nodal disease (HR 1.06 per involved node; p < 0.004) were associated with LR. The 8-year risk of LR was 2.8 % for node-negative patients and 5.2 % for node-positive patients. CONCLUSION: BCT yields favorable outcomes for the large majority of patients, although increased LR was observed among those with non-luminal-A subtypes, younger age, and increasing lymph node involvement. Risk factors for LR after BCT appear to be converging with those after mastectomy in the current era.