The prognostic significance of metastatic pattern in stage IV male breast cancer at initial diagnosis: a population-based study.

PURPOSE: Metastatic pattern (MP) is a prognostic factor in women with breast cancer. However, the prognostic significance of MP in male breast cancer patients remains unknown. METHODS: Using the SEER database, we gathered demographic information and disease characteristics for men diagnosed with de novo metastatic breast cancer from 2010 to 2017. Metastases to bone, brain, liver, and lung were used to define MP (bone-only, visceral, bone and visceral [BV], or other). Statistical analyses were performed to identify associations between overall survival (OS) and MP, as well as other patient and tumor features. We used multivariate logistic regression to evaluate factors associated with sites of metastases. RESULTS: We included 250 patients. MP distribution was bone = 38.8%, visceral = 14.8%, BV = 33.2%, and other = 13.2%. Median OS for each was bone = 33 months, visceral = 23 months, BV = 20 months, and other = 46 months (p = 0.046). Patients with brain metastases had significantly shorter OS compared with no brain metastases (median OS = 9 months vs. 30 months; p < 0.001). Compared with other subtypes, triple negative had the shortest OS (median 9 months, p < 0.001). Logistic regression modeling revealed that compared with HR+/HER2- breast cancers, HR-/HER2+ had higher odds of liver metastases and triple negative had higher odds of brain metastases. Patients younger than 50 years had a significantly greater risk of developing brain metastases. CONCLUSIONS: MP and tumor subtype can predict OS outcomes in men with metastatic breast cancer at diagnosis. Brain metastases confer very poor prognosis.

Prognostic factors and survival according to tumour subtype in women presenting with breast cancer brain metastases at initial diagnosis.

BACKGROUND: The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Hence, the prognostic assessment and management of these patients is very challenging. The aim of this study was to analyse the influence of tumour subtype compared with other prognostic factors in the survival of patients with BMIBCD. METHODS: We evaluated women with BMIBCD, reported to Surveillance, Epidemiology and End Results program from 2010 to 2013. Patients with other primary malignancy were excluded. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS). RESULTS: We included 740 patients. Median OS for the whole population was 10 months, and 20.7% of patients were alive at 36 months. Tumour subtype distribution was: 46.6% hormone receptor (HR)+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% triple-negative. Univariate analysis showed that the presence of liver metastases, lung metastases and triple-negative patients (median OS 6 months) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8), lobular histology (hazard ratio 2.08), triple-negative subtype (hazard ratio 2.25), liver metastases (hazard ratio 1.6) and unmarried patients (hazard ratio 1.39) had significantly shorter OS. CONCLUSIONS: Although the prognosis of patients with BMIBCD is generally poor, 20.7% were still alive 3 years after the diagnosis. There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases.

Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis.

PURPOSE: To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM). METHODS: We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM. RESULTS: We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2- tumors, triple-negative and HR-/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases. CONCLUSIONS: There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

Locoregional treatment and overall survival of men with T1a,b,cN0M0 breast cancer: A population-based study.

BACKGROUND: Male breast cancer (MaBC) is an understudied disease; information about locoregional treatment and outcomes in patients with early stage is unknown. We aimed to analyse patient characteristics, locoregional treatment and overall survival (OS) of T1a,b,cN0M0 male breast cancer. METHODS: We evaluated men with T1a,b,cN0M0 breast cancer reported to Surveillance, Epidemiology, and End Results program from 1988 to 2012. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. RESULTS: We included 1263 patients. Median age was 66 years (range 27-103). Median follow-up was 62 months (range 1-294). OS at 5 and 10 years were 85.1% and 66.5%, respectively. Distribution according to tumour sub-stage was: T1a 6.5%, T1b 20.7% and T1c 72.8%. Mastectomy was performed in >74% of patients of each tumour size group and overall 44.1% had >5 lymph nodes examined (LNE). Univariate analysis showed that patients with T1c, no surgery and 0 LNE had worse prognosis. In multivariate analysis, older age (hazard ratio [HR] 11.09), grade 3/4 tumours (HR 1.7), no surgery (HR 3.3), 0 LNE (HR 5.1) and unmarried patients (HR 1.7) had significantly shorter OS. There were no differences in OS between breast conservation versus mastectomy and 1-5 LNE versus > 5 LNE. CONCLUSION: Men with early breast cancer have a favourable OS. However, older age, higher grade, no breast surgery, no LNE and unmarried status emerged as poor prognostic characteristics. Efforts to decrease the high rates of mastectomy and extensive LNE should be taken given similar OS observed with breast conservation and 1-5 LNE, respectively.

Adjuvant systemic therapy in older women with breast cancer.

Breast cancer in the elderly is an increasing clinical problem. In addition, ~60% of deaths from breast cancer occur in women aged 65 years and older. Despite this, older women with breast cancer have been underrepresented in clinical trials, and this has led to less than optimal evidence to guide their therapy. The management of elderly women with early breast cancer is a complex process that requires careful evaluation of life expectancy, comorbidities, patient values, and risks and benefits of available treatment options. This review will focus on current adjuvant systemic therapy options for older women with breast cancer, discuss the principles in the decision-making process, and define the role of endocrine therapy, chemotherapy, and targeted agents.

Novel approaches to target HER2-positive breast cancer: trastuzumab emtansine.

The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast carcinomas. Prior to the development of targeted therapies, HER2-positive breast cancer was associated with more aggressive disease and poor prognosis. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that results from the combination of trastuzumab and DM1, a derivative of the antimicrotubule agent maytansine. This molecule has the ability to enhance cytotoxic drug delivery to specifically targeted cells that overexpress HER2, therefore, maximizing efficacy while sparing toxicity. In recent years, T-DM1 has shown to improve outcomes in metastatic HER2-positive breast cancer that is resistant to trastuzumab. In addition, T-DM1 is currently being tested in the neoadjuvant and adjuvant settings to identify patients who may benefit from this therapy. This review focuses on the mechanism of action, early and late-phase clinical trials, and ongoing studies of T-DM1 in HER2-positive breast cancer.

Prognostic factors in male breast cancer: a population-based study.

Prognostic factors in male breast cancer (MaBC) are controversial. The objective of this study was to analyze patient characteristics and prognostic factors in MaBC over the last decade. Using the Surveillance, Epidemiology, and End Results program, we extracted MaBC patients diagnosed between 2003 and 2012. Patient characteristics were compared between tumor grades. We conducted univariate and multivariate analyses to determine the effects of each prognostic variable on overall survival (OS). The study included 2992 patients. The majority had ductal (85 %), ER-positive (95.1 %), and PR-positive (86 %) breast cancer; however, only 12.4 % had grade I tumors. Stage I and II disease represented 73 % of cases. There was a significant association between grade III/IV tumors with ductal histology, ER and PR negativity, advanced stage, receipt of mastectomy and radiotherapy, and breast cancer death (all P < 0.05). ER-positive patients had better OS (hazard ratio 0.69, P = 0.03); however, after 7.5 years, OS rates by ER status were similar. In multivariate analysis, older age, grade III/IV tumors, stage IV disease, no surgery, no radiotherapy, ER-negative tumors, and unmarried patients had significantly shorter OS (all P < 0.05). Over the past decade, MaBC has been diagnosed most frequently with early stages of disease and high rates of ER positivity; however, grade I is uncommon. ER positivity is associated with better prognosis, mainly during the first 5 years after diagnosis. Age at diagnosis, tumor grade, stage, surgery, radiotherapy, ER, and marital status have clear impact on OS in MaBC.

Breast cancer brain metastases: the last frontier.

Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10-16 % of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Unfortunately, patients who develop brain metastases tend to have poor prognosis with short overall survival. In addition, brain metastases are a major cause of morbidity, associated with progressive neurologic deficits that result in a reduced quality of life. Tumor subtypes play a key role in prognosis and treatment selection. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. This review will focus on current treatment options, novel therapies, future approaches and ongoing clinical trials for patients with breast cancer brain metastases.

Prognostic significance of tumor subtypes in male breast cancer: a population-based study.

Substantial controversy exists about the prognostic role of tumor subtypes in male breast cancer (MaBC). The aim of this study was to analyze the characteristics of each tumor subtype in MaBC and its association with prognosis compared with other factors. We evaluated MaBC patients between 2010 and 2012 with known estrogen receptor, progesterone receptor [together hormone receptor (HR)] status, and human epidermal growth factor receptor 2 (HER2) status reported to the Surveillance, Epidemiology, and End Results program. Patients were classified as: HR-positive/HER2-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and triple-negative (TN). Univariate and multivariate analyses determined the effect of each variable on overall survival (OS). We included 960 patients. Patient distribution was 84.9 % HR-positive/HER2-negative, 11.6 % HR-positive/HER2-positive, 0.6 % HR-negative/HER2-positive, and 2.9 % TN. TN patients were younger, had higher grade, presented with more advanced stage, were more likely to have mastectomy, and to die of breast cancer (all P < 0.05). Univariate analysis showed that HER2 positivity was associated with shorter OS (hazard ratio 1.90, P = 0.031) and TN patients had worse prognosis (hazard ratio 5.10, P = 0.0004). In multivariate analysis, older patients (hazard ratio 3.10, P = 0.032), those with stage IV (hazard ratio 16.27, P < 0.001) and those with TN tumors (hazard ratio 4.61, P = 0.002) had significantly worse OS. We observed significant differences in patient characteristics according to tumor subtype. HER2-positive and TN represented a small proportion of cases. In addition to age and stage, tumor subtype has clear influence on OS in MaBC.

Sixteen years follow-up results of a randomized phase II trial of neoadjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) compared with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in stage III breast cancer: GOCS experience.

Neoadjuvant chemotherapy (NAC) allows direct evaluation of the tumor's sensitivity to therapy, eradication of micrometastatic disease and the possibility of performing breast conserving surgery. The aim of this study was to describe long-term results of NAC in stage III breast cancer patients. We evaluated 126 patients that participated in a phase II randomized trial of neoadjuvant FAC compared with CMF. Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Median follow-up was 4.5 years (range 0.2-16.4). Objective response rate (OR) was similar in both groups (61 % for FAC, 66 % for CMF, P = NS). There were no differences in median disease free survival (DFS) or overall survival (OS) (5.1 vs 3.3 years and 6.7 vs 6.3 years for FAC and CMF, respectively). After 16 years of follow-up, 53 patients are still alive. Multivariate analysis showed that the number of pathologically involved lymph nodes (pLN) was the only factor associated with both, DFS and OS (P = 0.0003 and P = 0.0005, respectively). Both regimens were well tolerated, CMF had higher incidence of grade 3-4 leukopenia, thrombocytopenia, and stomatitis, whereas alopecia was more common in FAC. To the best of our knowledge, this is the first study to report long-term outcomes of FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both regimens showed similar OR, long-term toxicity, DFS, and OS rate at 16 years. After 5 years, the hazard of death seems to decline. The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival.