Machine learning prediction of pathological complete response and overall survival of breast cancer patients in an underserved inner-city population.

BACKGROUND: Generalizability of predictive models for pathological complete response (pCR) and overall survival (OS) in breast cancer patients requires diverse datasets. This study employed four machine learning models to predict pCR and OS up to 7.5 years using data from a diverse and underserved inner-city population. METHODS: Demographics, staging, tumor subtypes, income, insurance status, and data from radiology reports were obtained from 475 breast cancer patients on neoadjuvant chemotherapy in an inner-city health system (01/01/2012 to 12/31/2021). Logistic regression, Neural Network, Random Forest, and Gradient Boosted Regression models were used to predict outcomes (pCR and OS) with fivefold cross validation. RESULTS: pCR was not associated with age, race, ethnicity, tumor staging, Nottingham grade, income, and insurance status (p > 0.05). ER-/HER2+ showed the highest pCR rate, followed by triple negative, ER+/HER2+, and ER+/HER2- (all p < 0.05), tumor size (p < 0.003) and background parenchymal enhancement (BPE) (p < 0.01). Machine learning models ranked ER+/HER2-, ER-/HER2+, tumor size, and BPE as top predictors of pCR (AUC = 0.74-0.76). OS was associated with race, pCR status, tumor subtype, and insurance status (p < 0.05), but not ethnicity and incomes (p > 0.05). Machine learning models ranked tumor stage, pCR, nodal stage, and triple-negative subtype as top predictors of OS (AUC = 0.83-0.85). When grouping race and ethnicity by tumor subtypes, neither OS nor pCR were different due to race and ethnicity for each tumor subtype (p > 0.05). CONCLUSION: Tumor subtypes and imaging characteristics were top predictors of pCR in our inner-city population. Insurance status, race, tumor subtypes and pCR were associated with OS. Machine learning models accurately predicted pCR and OS.

Adjuvant platinum versus capecitabine for residual, invasive, triple-negative breast cancer: Patient-reported outcomes in ECOG-ACRIN EA1131.

BACKGROUND: Patient-reported outcomes (PROs) are a better tool for evaluating the experiences of patients who have symptomatic, treatment-associated adverse events (AEs) compared with clinician-rated AEs. The authors present PROs assessing health-related quality of life (HRQoL) and treatment-related neurotoxicity for adjuvant capecitabine versus platinum on the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) EA1131 trial (ClinicalTrials.gov identifier NCT02445391). METHODS: Participants completed the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) and the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale (platinum arm only) at baseline, cycle 3 day 1 (C3D1), 6 months, and 15 months. Because of early termination, power was insufficient to test the hypothesis that HRQoL, as assessed by the NFBSI-16 treatment side-effect (TSE) subscale, would be better at 6 and 15 months in the capecitabine arm; all analyses were exploratory. Means were compared by using t-tests or the Wilcoxon rank-sum test, and proportions were compared by using the χ2 test. RESULTS: Two hundred ninety-six of 330 eligible patients provided PROs. The mean NFBSI-16 TSE subscale score was lower for the platinum arm at baseline (p = .02; absolute difference, 0.6 points) and for the capecitabine arm at C3D1 (p = .04; absolute difference, 0.5 points), but it did not differ at other times. The mean change in TSE subscale scores differed between the arms from baseline to C3D1 (platinum arm, 0.15; capecitabine arm, -0.72; p = .03), but not from baseline to later time points. The mean decline in Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale scores exceeded the minimal meaningful change (1.38 points) from baseline to each subsequent time point (all p < .05). CONCLUSIONS: Despite the similar frequency of clinician-rated AEs, PROs identified greater on-treatment symptom burden with capecitabine and complemented clinician-rated AEs by characterizing patients' experiences during chemotherapy.

Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer.

BACKGROUND: The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS: We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS: The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS: Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.

BACKGROUND: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. (Funded by the National Cancer Institute and others; TAILORx ClinicalTrials.gov number, NCT00310180 .).

Phase I/II trial of ruxolitinib in combination with trastuzumab in metastatic HER2 positive breast cancer.

PURPOSE: Preclinical data demonstrate STAT3 as an important regulator in HER2+ tumors, and disruption of the IL6-JAK2-STAT-S100A8/S100A9 signaling cascade reduces HER2+ cell viability. Ruxolitinib is an FDA approved inhibitor of JAK1 and JAK2. We performed a phase I/II trial investigating the safety and efficacy of the combination of trastuzumab and ruxolitinib in patients with trastuzumab-resistant metastatic HER2+ breast cancer. METHODS: Patients with metastatic HER2+ breast cancer progressing on at least 2 lines of HER2-directed therapy were eligible. The phase I portion determined the tolerable dose of ruxolitinib in combination with trastuzumab. The primary objective of the phase II was to assess the progression free survival (PFS) of the combination of ruxolitinib plus trastuzumab compared to historical control. RESULTS: Twenty-eight patients were enrolled, with a median number of prior therapies of 4.5. Ruxolitinib 25 mg twice daily was the recommended phase II dose with no dose limiting toxicities (DLTs). Of 26 evaluable patients in phase II, the median PFS was 8.3 weeks (95% CI 7.1, 13.9). Among the 14 patients with measurable disease, 1 patient had a partial response and 4 patients had stable disease. Most of the adverse events were hematologic. CONCLUSION: While well tolerated with a strong preclinical rationale, the combination of ruxolitinib and trastuzumab did not lead to an improvement in PFS compared to historical control in patients with trastuzumab-resistant metastatic HER2+ breast cancer.

Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.

BACKGROUND: Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. METHODS: We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). RESULTS: Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).

Progress in adjuvant chemotherapy for breast cancer: an overview.

Breast cancer is the most common cause of cancer and cancer death worldwide. Although most patients present with localized breast cancer and may be rendered disease-free with local therapy, distant recurrence is common and is the primary cause of death from the disease. Adjuvant systemic therapies are effective in reducing the risk of distant and local recurrence, including endocrine therapy, anti-HER2 therapy, and chemotherapy, even in patients at low risk of recurrence. The widespread use of adjuvant systemic therapy has contributed to reduced breast cancer mortality rates. Adjuvant cytotoxic chemotherapy regimens have evolved from single alkylating agents to polychemotherapy regimens incorporating anthracyclines and/or taxanes. This review summarizes key milestones in the evolution of adjuvant systemic therapy in general, and adjuvant chemotherapy in particular. Although adjuvant treatments are routinely guided by predictive factors for endocrine therapy (hormone receptor expression) and anti-HER2 therapy (HER2 overexpression), predicting benefit from chemotherapy has been more challenging. Randomized studies are now in progress utilizing multiparameter gene expression assays that may more accurately select patients most likely to benefit from adjuvant chemotherapy.

A phase I-II study of the histone deacetylase inhibitor vorinostat plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in locally advanced breast cancer.

Histone deacetylases (HDACs) are a family of enzymes that regulate chromatin remodeling and gene transcription. Vorinostat is a panHDAC inhibitor that sensitizes breast cancer cells to taxanes and trastuzumab by suppressing HDAC6 and Hsp90 client proteins. Fifty-five patients with clinical stage IIA-IIIC breast cancer received 12 weekly doses of paclitaxel (80 mg/m(2)) plus vorinostat (200-300 mg PO BID) on days 1-3 of each paclitaxel dose plus trastuzumab (for Her2/neu positive disease only), followed by doxorubicin/cyclophosphamide (60/600 mg/m(2) every 2 weeks plus pegfilgrastim). The primary study endpoint was pathologic complete response (pCR). pCR occurred in 13 of 24 evaluable patients with Her2-positive disease (54, 95 % confidence intervals [CI] 35-72 %), which met the prespecified study endpoint. pCR occurred in 4 of 15 patients with triple negative disease (27, 95 % CI 11-52 %) and none of 12 patients with ER-positive, Her2/neu negative disease (0, 95 % CI 0-24 %), which did not meet the prespecified endpoint. ER-positive tumors exhibited lower Ki67 and higher Hsp70 expression, and HDAC6, Hsp70, p21, and p27 expression were not predictive of response. Vorinostat increased acetylation of Hsp90 and alpha tubulin, and reduced expression of Hsp90 client proteins and HDAC6 in the primary tumor. Combination of vorinostat with weekly paclitaxel plus trastuzumab followed by doxorubicin-cyclophosphamide is associated with a high pCR rate in locally advanced Her2/neu positive breast cancer. Consistent with cell line and xenograft data, vorinostat increased acetylation of Hsp90 and alpha tubulin, and decreased Hsp90 client protein and HDAC6 expression in human breast cancers in vivo.

Taxanes: impact on breast cancer therapy.

Taxanes play an important role in the management of early-stage and advanced-stage breast cancer. Initial studies sought to determine whether there was antitumor activity in patients with metastatic disease, and identify the optimal agent, dose, and schedule. Subsequent studies established a role for both paclitaxel and docetaxel as adjuvant therapy, determined whether they should be administered concurrently or sequentially with other cytotoxic agents, and also determined the optimal agent, dose, and schedule. Taxanes have also been combined with biologic agents, including anti-HER2-directed therapy and antiangiogenic therapy. The aim of this article is to provide a review of pivotal trials evaluating taxane therapy that have informed the current approach for the use of taxanes in early-stage and advanced-stage breast cancer.

ECOG-ACRIN EAZ171: Prospective Validation Trial of Germline Predictors of Taxane-Induced Peripheral Neuropathy in Black Women With Early-Stage Breast Cancer.

PURPOSE: Black women experience higher rates of taxane-induced peripheral neuropathy (TIPN) compared with White women when receiving adjuvant once weekly paclitaxel for early-stage breast cancer, leading to more dose reductions and higher recurrence rates. EAZ171 aimed to prospectively validate germline predictors of TIPN and compare rates of TIPN and dose reductions in Black women receiving (neo)adjuvant once weekly paclitaxel and once every 3 weeks docetaxel for early-stage breast cancer. METHODS: Women with early-stage breast cancer who self-identified as Black and had intended to receive (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel were eligible, with planned accrual to 120 patients in each arm. Genotyping was performed to determine germline neuropathy risk. Grade 2-4 TIPN by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was compared between high- versus low-risk genotypes and between once weekly paclitaxel versus once every 3 weeks docetaxel within 1 year. Patient-rated TIPN and patient-reported outcomes were compared using patient-reported outcome (PRO)-CTCAE and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity. RESULTS: Two hundred and forty of 249 enrolled patients had genotype data, and 91 of 117 (77.8%) receiving once weekly paclitaxel and 87 of 118 (73.7%) receiving once every 3 weeks docetaxel were classified as high-risk. Physician-reported grade 2-4 TIPN was not significantly different in high- versus low-risk genotype groups with once weekly paclitaxel (47% v 35%; P = .27) or with once every 3 weeks docetaxel (28% v 19%; P = .47). Grade 2-4 TIPN was significantly higher in the once weekly paclitaxel versus once every 3 weeks docetaxel arm by both physician-rated CTCAE (45% v 29%; P = .02) and PRO-CTCAE (40% v 24%; P = .03). Patients receiving once weekly paclitaxel required more dose reductions because of TIPN (28% v 9%; P < .001) or any cause (39% v 25%; P = .02). CONCLUSION: Germline variation did not predict risk of TIPN in Black women receiving (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel. Once weekly paclitaxel was associated with significantly more grade 2-4 TIPN and required more dose reductions than once every 3 weeks docetaxel.

How do I treat inflammatory breast cancer?

Inflammatory breast cancer (IBC) is an uncommon and aggressive presentation of locally advanced breast cancer that is potentially curable when localized but may be associated with distant metastasis in up to one-third of patients at presentation. The diagnosis of IBC is made based on clinical features, including the presence of skin edema and erythema involving at least one-third of the breast, with or without a mass, and usually associated with dermal lymphatic invasion (DLI) on skin biopsy. Management requires combined modality therapy, including neoadjuvant chemotherapy with an anthracycline and taxane-based regimen, followed by surgery and radiotherapy, plus concurrent anti-HER2 therapy for HER2-positive disease, and endocrine therapy for at least 5 years after surgery for estrogen-receptor-positive disease (Fig. 1). There have been few large clinical trials focused on IBC; therefore, most data regarding treatment are derived from retrospective analyses, small studies, and extrapolation of results from trials of noninflammatory locally advanced breast cancer. Patients with IBC should be encouraged to enroll in clinical trials whenever possible. In addition, further research into the biology of IBC may help to elucidate the mechanisms underlying its aggressive clinical behavior and to assist in the development of therapies targeted for this specific population.

EZH2 Protein Expression in Triple-negative Breast Cancer Treated With Neoadjuvant Chemotherapy: An Exploratory Study of Association With Tumor Response and Prognosis.

INTRODUCTION: Neaodjuvant chemotherapy is used to treat high risk triple-negative breast cancer (TNBC). Residual cancer burden (RCB) is used to predict risk of relapse after neoadjuvant chemotherapy (NAC); however, it cannot predict disease recurrence with certainty. EZH2 is a targetable oncogenic protein overexpressed in TNBC and associated with metastasis and stem cell expansion. We quantified EZH2 protein expression in TNBC before NAC to examine potential utility as a predictive and prognostic biomarker. MATERIALS AND METHODS: We retrospectively identified 63 patients with localized TNBC treated with NAC. We quantified EZH2 nuclear expression in pretherapy biopsies using a score which included intensity and percent of positive cells at each intensity. EZH2 expression was evaluated as a continuous variable and dichotomized at a score of 210. Logistic regression analysis was used to determine association between EZH2 expression and RCB, tumor-infiltrating lymphocytes, clinicopathologic features and disease-free survival. RESULTS: There was no significant association between EZH2 score and posttreatment RCB class evaluated as a continuous variable (P=0.831) or dichotomized at 210 (P=0.546). On multivariable logistic regression, adjusted for covariates including RCB, EZH2 >210 was associated with development of metastasis (odds ratio=14.35, 95% confidence interval: 2.69-76.66; P=0.002). Logistic regression was run with EZH2 scores as a continuous variable and increased EZH2 score was associated with metastasis (odds ratio=1.10, 95% confidence interval: 1.00-1.03; P=0.047). CONCLUSION: In our study of TNBC treated with NAC, high EZH2 expression in pretherapy core biopsies was significantly associated with metastatic recurrence independent of RCB. The potential value of EZH2 as a biomarker to improve stratification of outcome after NAC should be explored further.

The 21-gene recurrence score in early non-ductal breast cancer: a National Cancer Database analysis.

The 21-gene recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit in early estrogen receptor-positive (ER +) HER2-negative (HER2-) breast cancer (BCA). We evaluated clinicopathologic characteristics, RS and chemotherapy benefit in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and carcinomas of mixed histologies (ductal + lobular (DLC), ductal + other (DOC), lobular + other (LOC)). Women diagnosed between 1/1/2010 and 1/1/2014 with ER + HER2- BCA, measuring <5 cm, with 0-3 involved axillary nodes, surgery as first treatment, and available RS, were identified from the NCDB. Associations between categorical variables were examined using chi-square test. Cox proportional hazards model was used to examine overall survival (OS) differences among histology subtypes. IDC was associated with smaller size, high grade, and RS > 26. ILC was associated with larger size, and least likely to be high grade (p < 0.0001). Lobular histology was associated with lower incidence of RS > 26. IDC patients (pts) were more likely to receive chemotherapy than pts with other histologies (p < 0.0001). OS for IDC, ILC and DOC were similar. DLC was associated with improved OS (HR 0.82, p = 0.02). Adjuvant chemotherapy was associated with improved OS in IDC (HR = 0.76, p < 0.0001) but not in ILC (HR = 0.99, p = 0.93), DLC (HR = 1.04, p = 0.86), DOC (HR = 0.87, p = 0.71), or LOC (HR = 2.91, p = 0.10). Lobular and mixed BCA histologies have distinct clinicopathologic features compared with IDC, and are less likely to have high RS. OS is similar for IDC and ILC. Although chemotherapy benefit was seen only in IDC, benefit for ILC with RS > 26 cannot be excluded.

EZH2 Protein Expression in Estrogen Receptor Positive Invasive Breast Cancer Treated With Neoadjuvant Endocrine Therapy: An Exploratory Study of Association With Tumor Response.

INTRODUCTION: Neoadjuvant endocrine therapy (NET) can be used to treat estrogen receptor positive (ER+) invasive breast cancer (IBC). Tumors with Ki67>10% after 2 to 4 weeks of NET are considered resistant to endocrine therapy. Enhancer of Zeste Homolog 2 (EZH2) is a targetable oncoprotein and overexpression in ER+ IBC has been linked to resistance to endocrine therapy. We examined whether EZH2 expression levels in ER+ IBC could be used to predict response to NET. MATERIALS AND METHODS: We retrospectively identified 46 patients with localized ER+ HER2/neu negative IBC treated with a minimum of 4 weeks of NET. We quantified EZH2 nuclear expression in pretherapy core biopsies using a score that included intensity and percent of cells staining. Ki67 was evaluated in both pretherapy core biopsies and posttherapy tumor resections and scored according to the guidelines of the International Ki67 Working Groups, with a global weighted score. Ki67≤10% after NET was considered endocrine responsive. Logistic regression analysis was performed to determine the association between EZH2 expression and response to NET. RESULTS: We found significant associations of tumor grade ( P =0.011), pretherapy Ki67 ( P =0.003), and EZH2 ( P <0.001), with response to NET. On logistic regression adjusted for tumor grade and pretherapy Ki67, increased EZH2 scores were associated with decreased odds of endocrine responsiveness, defined as posttreatment Ki67≤10% (odds ratio=0.976, 95% CI, 0.956 to 0.997; P =0.026). In addition, with EZH2 score in the model, associations of tumor grade and pretreatment Ki67 with posttreatment Ki67≤10% response to NET became not significant. CONCLUSIONS: Our results suggest that EZH2 might be a useful biomarker to predict response to NET.

An interactive mobile application versus an educational booklet to promote job retention in women undergoing adjuvant chemotherapy for breast cancer: a randomized controlled trial.

BACKGROUND: Job loss after a cancer diagnosis can lead to long-term financial toxicity and its attendant adverse clinical consequences, including decreased treatment adherence. Among women undergoing (neo)adjuvant chemotherapy for breast cancer, access to work accommodations (e.g., sick leave) is associated with higher job retention after treatment completion. However, low-income and/or minority women are less likely to have access to work accommodations and, therefore, are at higher risk of job loss. Given the time and transportation barriers that low-income working patients commonly face, it is crucial to develop an intervention that is convenient and easy to use. METHODS: We designed an intervention to promote job retention during and after (neo)adjuvant chemotherapy for breast cancer by improving access to relevant accommodations. Talking to Employers And Medical staff about Work (TEAMWork) is an English/Spanish mobile application (app) that provides (1) suggestions for work accommodations tailored to specific job demands, (2) coaching/strategies for negotiating with an employer, (3) advice for symptom self-management, and (4) tools to improve communication with the medical oncology team. This study is a randomized controlled trial to evaluate the app as a job-retention tool compared to a control condition that provides the app content in an informational paper booklet. The primary outcome of the study is work status after treatment completion. Secondary outcomes include work status 1 and 2 years later, participant self-efficacy to ask an employer for accommodations, receipt of workplace accommodations during and following adjuvant therapy, patient self-efficacy to communicate with the oncology provider, self-reported symptom burden during and following adjuvant therapy, and cancer treatment adherence. DISCUSSION: This study will assess the use of mobile technology to improve vulnerable breast cancer patients' ability to communicate with their employers and oncology providers, work during treatment and retain their jobs in the long term, thereby diminishing the potential consequences of job loss, including decreased treatment adherence, debt, and bankruptcy. TRIAL REGISTRATION: ClincalTrials.gov NCT03572374 . Registered on 08 June 2018.

The clinical utility of gene expression assays in breast cancer patients with 0-3 involved lymph nodes.

Multigene expression assays are prognostic for recurrence in hormone-receptor positive 2 (HER-2) negative breast cancer, and, in some cases, predictive of benefit from chemotherapy or extended endocrine therapy. The results of these assays may be used to guide treatment recommendations for early HER-2 negative breast cancer. We review the results of trials establishing the clinical utility of several commercially available gene expression assays.

Lymphovascular invasion, race, and the 21-gene recurrence score in early estrogen receptor-positive breast cancer.

Lymphovascular invasion (LVI) and Black race are associated with poorer prognosis in early breast cancer (EBC). We evaluated the association between LVI and race, and whether LVI adds prognostic benefit to the 21-gene recurrence score (RS) in EBC. Women with ER+ HER2- EBC measuring up to 5 cm, with 0-3 involved axillary nodes, diagnosed between 1 January 2010 and 1 January 2014, who underwent surgery as first treatment and had available RS, were identified in the NCDB database. Bivariate associations between two categorical variables were examined using chi-square test. Multivariate Cox proportional hazards model were used to assess the association of LVI, race, and other covariates with overall survival (OS). 77,425 women, 65,018 node-negative (N0), and 12,407 with 1-3 positive (N+) nodes, were included. LVI was present in 12.7%, and associated with poor grade, RS 26-100, and N+ (all p < 0.0001), but not Black race. In multivariate analysis, LVI was associated with worse OS in N0 [HR 1.37 (95% CI 1.27, 1.57], but not N+ EBC. LVI was associated with worse OS in N0 patients with RS 11-25 [HR 1.31 (95% CI 1.09, 1.57)] and ≥26 [HR 1.58 (95% CI 1.30, 1.93)], but not RS 0-10. No interaction between LVI and chemotherapy benefit was seen. Black race was associated with worse OS in N0 (HR 1.21, p = 0.009) and N+ (HR 1.37, p = 0.015) disease. LVI adds prognostic information in ER+, HER2-, N0 BCA with RS 11-100, but does not predict chemotherapy benefit. Black race is associated with worse OS, but not LVI.

Seroconversion rates following COVID-19 vaccination among patients with cancer.

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.

Evaluation of the Novel 4R Oncology Care Planning Model in Breast Cancer: Impact on Patient Self-Management and Care Delivery in Safety-Net and Non-Safety-Net Centers.

PURPOSE: Optimal cancer care requires patient self-management and coordinated timing and sequence of interdependent care. These are challenging, especially in safety-net settings treating underserved populations. We evaluated the 4R Oncology model (4R) of patient-facing care planning for impact on self-management and delivery of interdependent care at safety-net and non-safety-net institutions. METHODS: Ten institutions (five safety-net and five non-safety-net) evaluated the 4R intervention from 2017 to 2020 with patients with stage 0-III breast cancer. Data on self-management and care delivery were collected via surveys and compared between the intervention cohort and the historical cohort (diagnosed before 4R launch). 4R usefulness was assessed within the intervention cohort. RESULTS: Survey response rate was 63% (422/670) in intervention and 47% (466/992) in historical cohort. 4R usefulness was reported by 79.9% of patients receiving 4R and was higher for patients in safety-net than in non-safety-net centers (87.6%, 74.2%, P = .001). The intervention cohort measured significantly higher than historical cohort in five of seven self-management metrics, including clarity of care timing and sequence (71.3%, 55%, P < .001) and ability to manage care (78.9%, 72.1%, P = .02). Referrals to interdependent care were significantly higher in the intervention than in the historical cohort along all six metrics, including primary care consult (33.9%, 27.7%, P = .045) and flu vaccination (38.6%, 27.9%, P = .001). Referral completions were significantly higher in four of six metrics. For safety-net patients, improvements in most self-management and care delivery metrics were similar or higher than for non-safety-net patients, even after controlling for all other variables. CONCLUSION: 4R Oncology was useful to patients and significantly improved self-management and delivery of interdependent care, but gaps remain. Model enhancements and further evaluations are needed for broad adoption. Patients in safety-net settings benefited from 4R at similar or higher rates than non-safety-net patients, indicating that 4R may reduce care disparities.

Randomized Phase III Postoperative Trial of Platinum-Based Chemotherapy Versus Capecitabine in Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy: ECOG-ACRIN EA1131.

PURPOSE: Patients with triple-negative breast cancer (TNBC) and residual invasive disease (RD) after completion of neoadjuvant chemotherapy (NAC) have a high-risk for recurrence, which is reduced by adjuvant capecitabine. Preclinical models support the use of platinum agents in the TNBC basal subtype. The EA1131 trial hypothesized that invasive disease-free survival (iDFS) would not be inferior but improved in patients with basal subtype TNBC treated with adjuvant platinum compared with capecitabine. PATIENTS AND METHODS: Patients with clinical stage II or III TNBC with ≥ 1 cm RD in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine 14 out of 21 days every 3 weeks for six cycles. TNBC subtype (basal v nonbasal) was determined by PAM50 in the residual disease. A noninferiority design with superiority alternative was chosen, assuming a 4-year iDFS of 67% with capecitabine. RESULTS: Four hundred ten of planned 775 participants were randomly assigned to platinum or capecitabine between 2015 and 2021. After median follow-up of 20 months and 120 iDFS events (61% of full information) in the 308 (78%) patients with basal subtype TNBC, the 3-year iDFS for platinum was 42% (95% CI, 30 to 53) versus 49% (95% CI, 39 to 59) for capecitabine. Grade 3 and 4 toxicities were more common with platinum agents. The Data and Safety Monitoring Committee recommended stopping the trial as it was unlikely that further follow-up would show noninferiority or superiority of platinum. CONCLUSION: Platinum agents do not improve outcomes in patients with basal subtype TNBC RD post-NAC and are associated with more severe toxicity when compared with capecitabine. Participants had a lower than expected 3-year iDFS regardless of study treatment, highlighting the need for better therapies in this high-risk population.