Presentation, diagnosis, and management of the Li-Fraumeni syndrome.

Li-Fraumeni syndrome is a hereditary cancer syndrome that results in a dramatically increased risk of developing cancer over a patient's lifetime. Proper understanding of this syndrome is important for physicians across all specialties, as it can result in earlier cancer diagnosis and treatment. Here, we present the case of a patient presenting with Li-Fraumeni syndrome and discuss the appropriate screening recommendations and management of patients with this disorder.

Carcinoma en cuirasse.

Carcinoma en cuirasse (CeC) is an extremely rare form of cutaneous metastasis of breast cancer. Guidelines for diagnosis and treatment of CeC are limited due to the small number of reported cases. It can be difficult to distinguish CeC from benign etiologies on initial presentation, but CeC can be easily distinguished by histopathology. Treatment of CeC focuses on palliation with no consensus on therapy guidelines. Treatment modalities that have been explored include chemotherapy, radiotherapy (with or without local hyperthermia), and hormonal antagonists. Here we present a 62-year-old woman with recurrent triple-negative breast cancer manifesting as CeC to the chest wall.

Giant malignant phyllodes tumor with metastasis to the brain.

We present the case of a 32-year-old African American woman with a giant malignant phyllodes tumor that metastasized to the lungs and subsequently the brain. Her treatment included six cycles of adjuvant therapy with AIM (Adriamycin®, ifosfamide, and mesna) followed by therapy with gemcitabine and docetaxel. A grand mal seizure led to discovery of a 6 × 5 × 5 cm brain mass which was resected. After resection, the patient developed pulmonary edema, repeat seizure activity, and massive intrathoracic progression before succumbing to her disease. This is an unpredictable and understudied neoplasm that can be aggressive and fatal in rare cases.

Clinico-radiologic features and management of hematological tumors in the breast: a case series.

Hematological tumors arising in the breast are uncommon and require different treatment modalities dependent upon tumor type. Current treatment options include surgical excision, chemotherapy, and radiotherapy. Management of these breast malignancies are poorly outlined in the literature. The purpose of this case series is to report five cases consisting of extranodal marginal zone lymphoma, lymphoplasmacytic lymphoma, and extramedullary plasmacytoma occurring in the breast. The cases illustrate heterogeneous radiologic findings and varying management approaches to these tumors. The case series underscores the importance of having a wide differential at diagnosis and recognizes management of disease should be taken on an individual basis with consideration of prognosis and first-line treatment options.

Five-year results of a phase II trial of preoperative 5-fluorouracil, epirubicin, cyclophosphamide followed by docetaxel with capecitabine (wTX) (with trastuzumab in HER2-positive patients) for patients with stage II or III breast cancer.

We aimed to increase pathologic complete response (pCR) in patients with invasive breast cancer by adding preoperative capecitabine to docetaxel following 5-fluorouracil, epirubicin, cyclophosphamide (FEC) (with trastuzumab for patients with HER2-positive disease) and to evaluate 5-year disease-free survival (DFS) associated with this preoperative regimen. Chemotherapy included four cycles of FEC100 (5-fluorouracil 500 mg/m2 , epirubicin 100 mg/m2 , cyclophosphamide 500 mg/m2 IV on Day 1 every 21 days) followed by 4 21-day cycles of docetaxel (35 mg/m2  days 1 and 8) concurrently with capecitabine (825 mg/m2 orally twice daily for 14 days followed by 7 days off) (wTX). For HER2-positive patients, treatment was modified by decreasing epirubicin to 75 mg/m2 and adding trastuzumab (H) in standard doses (FEC75-H →wTX-H). The study objective was to achieve a pCR rate in the breast and axillary lymph nodes of 37% in patients with HER2-negative breast cancer and of 67% in patients with HER2-positive breast cancer treated with preoperative trastuzumab. A total of 186 patients were enrolled on study. In an intent-to-treat analysis, the pCR rate was 31% (37/118, 95% CI: 24-40%) in the HER2-negative patients, 24% (15/62, 95% CI: 14-37%) in ER-positive/HER2-negative patients, 39% (22/56, 95% CI: 27-53%) in the ER-negative/HER2-negative patients, and 46% (29/63, 95% CI: 34-48%) in the HER2-positive patients. The pCR rate in the 40 trastuzumab-treated patients was 53% (21/40, 95% CI: 38-67%). Grade 3 and 4 adverse events included neutropenia, leukopenia, diarrhea, and hand-foot skin reactions. One trastuzumab-treated patient developed grade 3 cardiotoxicity, and 4 others experienced grade 1-2 decrements in left ventricular function; all five patients' cardiac function returned to their baseline upon completion of trastuzumab. At 5 years, disease-free survival was 70% in the HER2-negative population (78% in ER-positive/HER2-negative and 62% in the ER-negative/HER2-negative patients) and 80% in the HER2-positive patients (87% in the trastuzumab-treated HER2-positive patients). At 5 years, overall survival was 80% in the HER2-negative population (88% in ER-positive/HER2-negative and 71% in the ER-negative/HER2-negative patients) and 86% in the HER2-positive patients (94.5% in the trastuzumab-treated HER2-positive patients). FEC100 (FEC75 with trastuzumab) followed by weekly docetaxel plus capecitabine, with or without trastuzumab is a safe, effective preoperative cytotoxic regimen. However, the addition of capecitabine to docetaxel following FEC, with or without trastuzumab, did not increase pCR rates nor 5-year DFS over the rates that have been reported with standard preoperative doxorubicin/cyclophosphamide (AC) followed by paclitaxel, with or without trastuzumab. Therefore, the use of capecitabine as part of preoperative chemotherapy is not recommended.

Two cancers in one: breast carcinoma with underlying melanoma.

A 61-year-old woman presented with a diagnosis of metastatic invasive lobular carcinoma of the right breast, and after treatment it had regressed or was stable except for a scalp nodule. When biopsied, the outer edges of the scalp lesion had findings consistent with breast carcinoma; however, the bulk of the tumor's pathology was consistent with melanoma. It appeared that most of the tumor was a highly vascularized melanoma with lobular breast carcinoma noted at its edges.

Patients with Slowly Proliferative Early Breast Cancer Have Low Five-Year Recurrence Rates in a Phase III Adjuvant Trial of Capecitabine.

PURPOSE: We conducted a randomized phase III study to determine whether patients with early breast cancer would benefit from the addition of capecitabine (X) to a standard regimen of doxorubicin (A) plus cyclophosphamide (C) followed by docetaxel (T). EXPERIMENTAL DESIGN: Treatment comprised eight cycles of AC→T (T dose: 100 mg/m(2) on day 1) or AC→XT (X dose: 825 mg/m(2) twice daily, days 1-14; T dose: 75 mg/m(2) on day 1). The primary endpoint was 5-year disease-free survival (DFS). RESULTS: Of 2,611 women, 1,304 were randomly assigned to receive AC→T and 1,307 to receive AC→XT. After a median follow-up of 5 years, the study failed to meet its primary endpoint [HR, 0.84; 95% confidence interval (CI), 0.67-1.05; P = 0.125]. A significant improvement in overall survival, a secondary endpoint, was seen with AC→XT versus AC→T (HR, 0.68; 95% CI, 0.51-0.92; P = 0.011). There were no unexpected adverse events. Of patients with estrogen receptor (ER)-positive/HER2-negative disease, 70% of whom were node-positive, 26% and 59% had tumors with a centrally assessed Ki-67 score of <10% or <20%, respectively, and only 17 (2%) and 53 (6%) DFS events, respectively, occurred in these groups at 7 years. CONCLUSIONS: The very low event rate in patients with ER-positive, low Ki-67 cancers, regardless of nodal status, strongly suggests that these patients should not be enrolled in adjuvant trials that assess 5-year DFS rates and that central Ki-67 analyses can identify these patients.

Genomic alterations in DNA repair and chromatin remodeling genes in estrogen receptor-positive metastatic breast cancer patients with exceptional responses to capecitabine.

We analyzed the genomic and phosphoproteomic profiles of breast cancer tissue obtained from six patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer who had highly durable (≥ 5 years) and, in some cases, ongoing clinical responses with capecitabine. Formalin-fixed, paraffin-embedded tissue samples from patients' primary (n = 4) or metastatic (n = 2) breast cancers were utilized for targeted next-generation sequencing and reversed phase protein microarray. Two patients received capecitabine monotherapy. Four patients received capecitabine in combination with paclitaxel; three of these continued single-agent capecitabine after stopping paclitaxel. Capecitabine was discontinued for progressive disease after a mean of 66 months in four patients (range 54-86 months), and two patients remain on therapy, having received capecitabine for >91 months and >122 months, respectively. Three patients' cancers (50%) had likely functional alterations in DNA repair and chromatin remodeling genes, while three other patients' cancers had variants of unknown significance in these pathways. Mutations in PIK3CA, amplifications of FGFR1 or ZNF703, or phosphorylation of HER family receptors and their downstream proteins did not preclude exceptional responses to capecitabine. None of the patients' tumors harbored TP53 or PTEN mutations. Four of the patients had breast cancer tissue available for PTEN immunohistochemistry, and all four patients' cancers were positive for PTEN. These surprising findings in a group of phenotypically similar patients with ER-positive, endocrine therapy-pretreated, HER2-negative metastases, are supported by preclinical data showing that sensitivity to 5-fluorouracil is enhanced by deficiencies in chromatin remodeling and homologous recombination genes. Our findings suggest that mutations that inactivate homologous recombination and/or chromatin remodeling genes within ER-positive, HER2-negative breast cancers may predict for highly durable responses to capecitabine.

Satisfaction with work-life balance and the career and retirement plans of US oncologists.

PURPOSE: To evaluate satisfaction with work-life balance (WLB) and career plans of US oncologists. METHODS: The American Society of Clinical Oncology conducted a survey of US oncologists evaluating satisfaction with WLB and career plans between October 2012 and March 2013. The sample included equal numbers of men and women from all career stages. RESULTS: Of 2,998 oncologists contacted, 1,490 (49.7%) returned surveys. From 1,117 oncologists (37.3% of overall sample) completing full-length surveys, we evaluated satisfaction with WLB and career plans among the 1,058 who were not yet retired. The proportion of oncologists satisfied with WLB (n = 345; 33.4%) ranked lower than that reported for all other medical specialties in a recent national study. Regarding career plans, 270 oncologists (26.5%) reported a moderate or higher likelihood of reducing their clinical work hours in the next 12 months, 351 (34.3%) indicated a moderate or higher likelihood of leaving their current position within 24 months, and 273 (28.5%) planned to retire before 65 years of age. Multivariable analyses found women oncologists (odds ratio [OR], 0.458; P < .001) and those who devoted greater time to patient care (OR for each additional hour, 0.977; P < .001) were less likely to be satisfied with WLB. Satisfaction with WLB and burnout were the strongest predictors of intent to reduce clinical work hours and leave current position on multivariable analysis. CONCLUSION: Satisfaction with WLB among US oncologists seems lower than for other medical specialties. Dissatisfaction with WLB shows a strong relationship with plans to reduce hours and leave current practice. Given the pending US oncologist shortage, additional studies exploring interactions among WLB, burnout, and career satisfaction and their impact on career and retirement plans are warranted.

Burnout and career satisfaction among US oncologists.

PURPOSE: To evaluate the personal and professional characteristics associated with career satisfaction and burnout among US oncologists. METHODS: Between October 2012 and March 2013, the American Society of Clinical Oncology conducted a survey of US oncologists evaluating burnout and career satisfaction. The survey sample included equal numbers of men and women and represented all career stages. RESULTS: Of 2,998 oncologists contacted, 1,490 (49.7%) returned surveys (median age of respondents, 52 years; 49.6% women). Among the 1,117 oncologists (37.3% of overall sample) who completed full-length surveys, 377 (33.8%) were in academic practice (AP) and 482 (43.2%) in private practice (PP), with the remainder in other settings. Oncologists worked an average of 57.6 hours per week (AP, 58.6 hours per week; PP, 62.9 hours per week) and saw a mean of 52 outpatients per week. Overall, 484 oncologists (44.7%) were burned out on the emotional exhaustion and/or depersonalization domain of Maslach Burnout Inventory (AP, 45.9%; PP, 50.5%; P = .18). Hours per week devoted to direct patient care was the dominant professional predictor of burnout for both PP and AP oncologists on univariable and multivariable analyses. Although a majority of oncologists were satisfied with their career (82.5%) and specialty (80.4%) choices, both measures of career satisfaction were lower for those in PP relative to AP (all P < .006). CONCLUSION: Overall career satisfaction is high among US oncologists, albeit lower for those in PP relative to AP. Burnout rates among oncologists seem similar to those described in recent studies of US physicians in general. Those oncologists who devote the greatest amount of their professional time to patient care seem to be at greatest risk for burnout.

Pathologic complete response after preoperative anti-HER2 therapy correlates with alterations in PTEN, FOXO, phosphorylated Stat5, and autophagy protein signaling.

BACKGROUND: To define protein molecular characteristics of tumor cells prior to, and immediately following, preoperative human epidermal growth factor receptor 2 (HER2)-targeted therapy that correlate with pathologic complete response (pCR) or non response (no pCR) to preoperative HER2-directed therapy and chemotherapy. METHODS: This open-label, phase II study randomized patients with HER2-positive stage II or III invasive breast cancer to trastuzumab, lapatinib, or both, 2 weeks prior to and during chemotherapy with FEC75 for 4 courses; then paclitaxel 80 mg/m2 weekly for 12 courses, then surgery. Core needle biopsies were collected at baseline and after 2 weeks of anti-HER2 therapy prior to chemotherapy. Data were correlated with pCR, defined as absence of invasive tumor in breast and lymph nodes. RESULTS: Of 100 enrolled patients, the analysis population included those who had surgery and received ≥75% chemotherapy (78% [n=78]). pCRs by arm are: trastuzumab (n=26), 54% [n=14]; lapatinib (n=29), 45% [n=13]; trastuzumab plus lapatinib (n=23), 74% [n=17]). Paired biopsy specimens were available for 49 patients (63%). Tumor cells of patients with pCR in the trastuzumab or lapatinib treatment arms showed nonphosphorylated FOXO, phosphorylated Stat5, and sparse signal-transduction protein network crosstalk representing different patterns of connections with PI3K and autophagy proteins compared with no pCR. CONCLUSION: In this exploratory study, pCR with preoperative anti-HER2 therapy and chemotherapy correlated with the levels and phosphorylation status of specific baseline signal pathway proteins in tumor cells. These data may provide candidate biomarkers to stratify initial treatment and potential combination therapies for future study. Tissue preservation technology introduced here makes this procedure widely feasible. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00524303.

Our experience as a Health Volunteers Overseas-sponsored team in Huê´, Vietnam.

A group from Texas Oncology and Baylor Charles A. Sammons Cancer Center traveled to Huê´, Vietnam, as part of Health Volunteers Overseas. From February 21 to March 6, 2012, five Baylor Sammons medical oncologists and an oncology nurse worked with a medical oncologist and a surgeon at the Huê´ College of Medicine and Pharmacy, suggesting approaches based on available resources. The two groups worked together to find optimal solutions for the patients. What stood out the most for the Baylor Sammons group was the Huê´ team's remarkable work ethic, empathy for patients, and treatment resourcefulness. The Baylor Sammons group also identified several unmet needs that could potentially be addressed by future volunteers in Huê´, including creation of an outpatient hospice program, establishment of breast cancer screening, modernization of the pathology department, instruction in and better utilization of pain management, better use of clinic space, and the teaching of oncology and English to medical students. There was a mutual exchange of knowledge between the two medical teams. The Baylor Sammons group not only taught but also learned how to take good care of patients with limited resources.

Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers.

The mutation pattern of breast cancer molecular subtypes is incompletely understood. The purpose of this study was to identify mutations in genes that may be targeted with currently available investigational drugs in the three major breast cancer subtypes (ER+/HER2-, HER2+, and Triple Negative). We extracted DNA from fine needle aspirations of 267 stage I-III breast cancers. These tumor specimens typically consisted of >80% neoplastic cells. We examined 28 genes for 163 known cancer-related nucleic acid variations by Sequenom technology. We observed at least one mutation in 38 alleles corresponding to 15 genes in 108 (40%) samples, including PIK3CA (16.1% of all samples), FBXW7 (8%), BRAF (3.0%), EGFR (2.6%), AKT1 and CTNNB1 (1.9% each), KIT and KRAS (1.5% each), and PDGFR-α (1.1%). We also checked for the polymorphism in PHLPP2 that is known to activate AKT and it was found at 13.5% of the patient samples. PIK3CA mutations were more frequent in estrogen receptor-positive cancers compared to triple negative breast cancer (TNBC) (19 vs. 8%, p=0.001). High frequency of PIK3CA mutations (28%) were also found in HER2+ breast tumors. In TNBC, FBXW7 mutations were significantly more frequent compared to ER+ tumors (13 vs. 5%, p=0.037). We performed validation for all mutated alleles with allele-specific PCR or direct sequencing; alleles analyzed by two different sequencing techniques showed 95-100% concordance for mutation status. In conclusion, different breast cancer subtypes harbor different type of mutations and approximately 40 % of tumors contained individually rare mutations in signaling pathways that can be potentially targeted with drugs. Simultaneous testing of many different mutations in a single needle biopsy is feasible and allows the design of prospective clinical trials that could test the functional importance of these mutations in the future.

Dose-dense doxorubicin and cyclophosphamide followed by dose-dense albumin-bound paclitaxel plus bevacizumab is safe as adjuvant therapy in patients with early stage breast cancer.

UNLABELLED: Every-2-week (dose-dense) adjuvant doxorubicin (A) plus cyclophosphamide (C) followed by cremophor-formulated paclitaxel (cf-P) was efficacious in metastatic breast cancer (BC). Albumin-bound paclitaxel (ab-P) was safe and more effective than cf-P, and the addition of bevacizumab to cf-P improved efficacy. This study compared the safety of dose-dense ab-P vs cf-P plus bevacizumab following dose-dense adjuvant AC for early-stage BC. PATIENTS AND METHODS: Women with operable, histologically confirmed BC were randomized to 4 cycles of dose-dense A 60 mg/m(2) plus C 600 mg/m(2) IV with SC pegfilgrastim, followed by 4 cycles of either dose-dense IV ab-P 260 mg/m(2) or cf-P 175 mg/m(2). Bevacizumab was given during and following chemotherapy. 97 and 96% of patients completed 4 cycles of AC therapy, while 84 and 85% of patients completed 4 cycles of taxane therapy in the ab-P and cf-P arms, respectively (N = 197). Baseline patient characteristics were similar. The most common grade ≥3 taxane-related adverse events (AEs) were fatigue and neutropenia. Dose reductions were similar between the treatment arms. During AC therapy, the majority of dose reductions were due to febrile neutropenia; during taxane therapy, the majority of cases were due to neuropathy. No taxane-related dose interruption occurred in the ab-P arm, while 3 occurred in the cf-P arm due to hypersensitivity reactions. The mean cumulative paclitaxel dose was 950.5 and 660.8 mg/m(2) in the ab-P and cf-P arms, respectively. A 44% higher paclitaxel dose was delivered in the ab-P compared with the cf-P arm (P < 0.0001), while achieving a similar safety profile. ab-P plus bevacizumab following AC therapy without prophylactic premedications was tolerable in early-stage BC patients.

The sensitivity and specificity of sentinel lymph node biopsy for breast cancer at Baylor University Medical Center at Dallas: a retrospective review of 488 cases.

Sentinel lymph node (SLN) biopsy has become the standard of care for breast carcinoma management, as it precludes the negative morbid effects-including decreased shoulder range of motion, lymphedema, and paresthesias-of unnecessary axillary lymph node dissection. However, the method of pathologic evaluation of the lymph node has been scrutinized to obtain the greatest sensitivity, specificity, and negative predictive value, ultimately for the benefit of the patient. This retrospective study analyzed 488 biopsies completed by two surgeons and read by multiple pathologists affiliated with Pathologists Biomedical Laboratories. When metastatic disease was not grossly obvious, analysis of the SLN began with touch imprint cytology and, if necessary, a frozen section analysis. On the subsequent day, three levels of the SLN were analyzed with hematoxylin and eosin stain and immunohistochemistry with cytokeratin AE1-3 and the appropriate control. Touch imprint cytology and/or frozen section analysis (where applicable) correctly identified 78 of 89 macrometastases, with a sensitivity of 88%, specificity of 100%, and negative predictive value of 97%. Sensitivity was 72% for micrometastases and 60% for isolated tumor cells, each with 100% specificity. In conclusion, the sensitivity and specificity of SLN biopsy at our institution compares with the higher end of percentages reported in the literature.

Iniparib plus chemotherapy in metastatic triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancers have inherent defects in DNA repair, making this cancer a rational target for therapy based on poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition. METHODS: We conducted an open-label, phase 2 study to compare the efficacy and safety of gemcitabine and carboplatin with or without iniparib, a small molecule with PARP-inhibitory activity, in patients with metastatic triple-negative breast cancer. A total of 123 patients were randomly assigned to receive gemcitabine (1000 mg per square meter of body-surface area) and carboplatin (at a dose equivalent to an area under the concentration-time curve of 2) on days 1 and 8--with or without iniparib (at a dose of 5.6 mg per kilogram of body weight) on days 1, 4, 8, and 11--every 21 days. Primary end points were the rate of clinical benefit (i.e., the rate of objective response [complete or partial response] plus the rate of stable disease for ≥6 months) and safety. Additional end points included the rate of objective response, progression-free survival, and overall survival. RESULTS: The addition of iniparib to gemcitabine and carboplatin improved the rate of clinical benefit from 34% to 56% (P=0.01) and the rate of overall response from 32% to 52% (P=0.02). The addition of iniparib also prolonged the median progression-free survival from 3.6 months to 5.9 months (hazard ratio for progression, 0.59; P=0.01) and the median overall survival from 7.7 months to 12.3 months (hazard ratio for death, 0.57; P=0.01). The most frequent grade 3 or 4 adverse events in either treatment group included neutropenia, thrombocytopenia, anemia, fatigue or asthenia, leukopenia, and increased alanine aminotransferase level. No significant difference was seen between the two groups in the rate of adverse events. CONCLUSIONS: The addition of iniparib to chemotherapy improved the clinical benefit and survival of patients with metastatic triple-negative breast cancer without significantly increased toxic effects. On the basis of these results, a phase 3 trial adequately powered to evaluate overall survival and progression-free survival is being conducted. (Funded by BiPar Sciences [now owned by Sanofi-Aventis]; ClinicalTrials.gov number, NCT00540358.).

Gene pathways associated with prognosis and chemotherapy sensitivity in molecular subtypes of breast cancer.

BACKGROUND: We hypothesized that distinct biological processes might be associated with prognosis and chemotherapy sensitivity in the different types of breast cancers. METHODS: We performed gene set analyses with BRB-ArrayTools statistical software including 2331 functionally annotated gene sets (ie, lists of genes that correspond to a particular biological pathway or biochemical function) assembled from Ingenuity Pathway Analysis and Gene Ontology databases corresponding to almost all known biological processes. Gene set analysis was performed on gene expression data from three cohorts of 234, 170, and 175 patients with HER2-normal lymph node-negative breast cancer who received no systemic adjuvant therapy to identify gene sets associated prognosis and three additional cohorts of 198, 85, and 62 patients with HER2-normal stage I-III breast cancer who received preoperative chemotherapy to identify gene sets associated with pathological complete response to therapy. These analyses were performed separately for estrogen receptor (ER)-positive and ER-negative breast cancers. Interaction between gene sets and survival and treatment response by breast cancer subtype was assessed in individual datasets and also in pooled datasets. Statistical significance was estimated with permutation test. All statistical tests were two-sided. RESULTS: For ER-positive cancers, from 370 to 434 gene sets were associated with prognosis (P ≤ .05) and from 209 to 267 gene sets were associated with chemotherapy response in analysis by individual dataset. For ER-positive cancers, 131 gene sets were associated with prognosis and 69 were associated with pathological complete response (P ≤.001) in pooled analysis. Increased expression of cell cycle-related gene sets was associated with poor prognosis, and B-cell immunity-related gene sets were associated with good prognosis. For ER-negative cancers, from 175 to 288 gene sets were associated with prognosis and from 212 to 285 gene sets were associated with chemotherapy response. In pooled analyses of ER-negative cancers, 14 gene sets were associated with prognosis and 23 were associated with response. Gene sets involved in sphingolipid and glycolipid metabolism were associated with better prognosis and those involved in base excision repair, cell aging, and spindle microtubule regulation were associated with chemotherapy response. CONCLUSION: Different biological processes were associated with prognosis and chemotherapy response in ER-positive and ER-negative breast cancers.