Tumor histological subtyping determined by hormone receptors and HER2 status defines different pathological complete response and outcome to dose-dense neoadjuvant chemotherapy in breast cancer patients

Purpose

To assess the impact in pathological complete response (pCR) and outcome of two dose-dense neoadjuvant chemotherapy (DDNC) regimens among different histological subtypes determined by hormonal receptor (HR) and HER2 status in breast cancer patients.

Methods

A total of 127 breast cancer patients were treated with DDNC in two prospective studies. A: adriamycin 40 mg/m² on day (d) 1 plus paclitaxel 150 mg/m² and gemcitabine 2,000 mg/m² on d2 for six cycles (n = 54). B: epirubicin 90 mg/m², cyclophosphamide 600 mg/m² on d1 for three cycles, followed by paclitaxel 150 mg/m² and gemcitabine 2,500 mg/m² on d1 ± trastuzumab according to HER2 status (n = 73). Histological subtypes of breast cancer were 49 % HR+/HER2?, 17.5 % HR+/HER2+, 13.5 % HR?/HER2+ and 20 % HR?/HER2?.

Results

pCR (absence of invasive cells in breast and lymph node) was achieved in 35 patients (28 %). The pCR rate was significantly different between histological subtypes: HR+/HER2? (9 %), HR+/HER2+ (23 %), HR?/HER2+ (50 %), HR?/HER2? (56 %) (p < 0.001). The median follow-up was 81 months (r: 15–150 months). HR?/HER2? tumor subtype had a significantly worse DFS compared to HR+/HER2? (p = 0.02), RH+/HER2+ (p = 0.04) and HR?/HER2+ tumor subtypes (p = 0.02). HR?/HER2? tumor subtype had a significantly shorter OS compared to HR+/HER2? (p = 0.007), RH+/HER2+ (p = 0.05), and HR?/HER2+ (p = 0.03) tumor subtypes. However, no significant difference was observed in DFS and OS among HR?/HER2? tumors that achieved a pCR.

Conclusions

HR?/HER2? and HR?/HER2+ subtypes had a high pCR rate to DDNC. HR?/HER2? tumors had a worse outcome compared to other tumor subtypes but no significant difference was observed among HR?/HER2? tumors that achieved a pCR.     

African American patients with breast cancer have worse prognosis than white patients in certain subtypes and stages

Purpose

Racial disparity of breast cancer in each subtype and substage is not clear.

Methods

We reviewed 156,938 patients with breast cancer from 2010 to 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Breast cancer was subtyped by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status as HR+/HER2?, HR+/HER2+, HR?/HER2+, and HR?/HER2?.

Results

African American (AA) patients had worse overall survival (OS) and breast cancer cause-specific survival (BCSS) in HR+/HER2? stages III and IV breast cancer and HR?/HER2+ stage IV cancer; they had worse OS but not BCSS in HR+ /HER2? stage II cancer and HR?/HER2? stage II cancer.

Conclusion

AA patients with breast cancer had worse survival in certain subtype and stage, especially in ER+ breast cancer.

     

Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2-positive subtype is associated with the most favorable outcome

Contrary to the situation in early breast cancer, little is known about the prognostic relevance of the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) in metastatic breast cancer. The objectives of this study were to present survival estimates and to determine the prognostic impact of breast cancer subtypes based on HR and HER2 status in a recent cohort of metastatic breast cancer patients, which is representative of current clinical practice. Patients diagnosed with metastatic breast cancer between 2007 and 2009 were included. Information regarding patient and tumor characteristics and treatment was collected. Patients were categorized in four subtypes based on the HR and HER2 status of the primary tumor: HR positive (+)/HER2 negative (?), HR+/HER2+, HR?/HER2+ and triple negative (TN). Survival was estimated using the Kaplan–Meier method. Cox proportional hazards model was used to determine the prognostic impact of breast cancer subtype, adjusted for possible confounders. Median follow-up was 21.8 months for the 815 metastatic breast cancer patients included; 66 % of patients had the HR+/HER2? subtype, 8 % the HR?/HER2+ subtype, 15 % the TN subtype and 11 % the HR+/HER2+ subtype. The longest survival was observed for the HR+/HER2+ subtype (median 34.4 months), compared to 24.8 months for the HR+/HER2? subtype, 19.8 months for the HR?/HER2+ subtype and 8.8 months for the TN subtype (P < 0.0001). In the multivariate analysis, subtype was an independent prognostic factor, as were initial site of metastases and metastatic-free interval. The HR+/HER2+ subtype was associated with the longest survival after diagnosis of distant metastases.     

HER3 status by immunohistochemistry is correlated with poor prognosis in hormone receptor-negative breast cancer patients

Breast cancer is a highly heterogeneous malignancy. The triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer subtypes are highly aggressive and are associated with a poor prognosis. The therapeutic targets for TNBC remain undefined, and many patients with the HER2 subtype acquire resistance to therapy after prolonged treatment. The objective of this study was to evaluate the prognostic significance of HER3 expression in invasive breast carcinoma. We established matched tissue microarray (TMA) blocks and clinical data from 950 cases of invasive breast carcinoma with long-term clinical follow-up data (median 109.7 months). Using the TMAs, we characterized the expression of ER, PR, HER2, EGFR, and HER3 by immunohistochemistry. Each case was classified as one of four IHC-based subtypes based on the expression of hormonal receptor (HR) and HER2. The clinicopathological characteristics and survival of 950 patients were analyzed by subtype. In the TNBC subtype, the HER3(+) group showed poorer disease-free survival (DFS, P = 0.010) and overall survival (OS, P = 0.015) than the HER3(?) group. In the HER2 subtype, the HER3(+) group also showed poorer DFS (P = 0.022) and OS (P = 0.077) than the HER3(?) group. However, there was no difference in patients with HR-positive breast cancer. HER3 expression was associated with poor DFS in both the TNBC and HER2 subtypes and poor OS in the TNBC subtype. HER3 overexpression is an important prognostic marker in hormone receptor-negative breast cancer, and further study is needed to clarify the role of HER-3 targeted treatment.     

Management of small T1a/b breast cancer by tumor subtype

Background

The treatment of patients with small (T1a/b) breast cancer is based on retrospective analysis. The influence of intrinsic tumor subtypes on patients’ outcome and treatment decision remains unclear.

Patients and methods

This is a prospective cohort register study including 1008 patients with small T1a/b breast cancer treated between 2003 and 2011. Tumors were grouped by biological characteristics into four different subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer (TNBC).

Results

The median follow-up time was 6.5 years. From 919 eligible patients, 408 (44.4%) were classified as luminal A, 246 (26.8%) as luminal B, 183 (19.9%) as HER2 enriched, and 82 (8.9%) as TNBC. A total of 305 (34.2%) patients were treated with systemic therapy. Patients receiving systemic therapy were significantly younger and had lymph node metastasis, higher tumor grade, negative HR, and positive HER2 status. Patients with luminal A tumors demonstrated the best survival rate which improved with systemic therapy. The survival rate of patients with luminal B cancer, HER2-enriched tumors, and TNBC improved by addition of systemic treatment. The effect of systemic treatment was significant in luminal B (p = 0.040) and HER2 overexpressing tumors (p = 0.016). The treatment effect of systemic therapy in HER2-enriched tumors remained significant even after adjustment of other prognostic factors (HR 0.43, CI 0.19–0.98; p = 0.047). Notably, tumor size was not associated with patients’ survival and treatment decision.

Conclusion

The treatment decision of small breast cancer should be made by biological subtype and not by tumor size or lymph node status.

     

Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases

Introduction

Activation status of the phosphatidylinositol 3-kinase (PI3K) pathway in breast cancer brain metastases (BCBMs) is largely unknown. We examined expression of phospho(p)-AKT, p-S6, and phosphatase and tensin homologue (PTEN) in BCBMs and their implications for overall survival (OS) and survival after BCBMs. Secondary analyses included PI3K pathway activation status and associations with time to distant recurrence (TTDR) and time to BCBMs. Similar analyses were also conducted among the subset of patients with triple-negative BCBMs.

Methods

p-AKT, p-S6, and PTEN expression was assessed with immunohistochemistry in 52 BCBMs and 12 matched primary BCs. Subtypes were defined as hormone receptor (HR)+/HER2-, HER2+, and triple-negative (TNBC). Survival analyses were performed by using a Cox model, and survival curves were estimated with the Kaplan-Meier method.

Results

Expression of p-AKT and p-S6 and lack of PTEN (PTEN-) was observed in 75%, 69%, and 25% of BCBMs. Concordance between primary BCs and matched BCBMs was 67% for p-AKT, 58% for p-S6, and 83% for PTEN. PTEN- was more common in TNBC compared with HR+/HER2- and HER2+. Expression of p-AKT, p-S6, and PTEN- was not associated with OS or survival after BCBMs (all, P > 0.06). Interestingly, among all patients, PTEN- correlated with shorter time to distant and brain recurrence. Among patients with TNBC, PTEN- in BCBMs was associated with poorer overall survival.

Conclusions

The PI3K pathway is active in most BCBMs regardless of subtype. Inhibition of this pathway represents a promising therapeutic strategy for patients with BCBMs, a group of patients with poor prognosis and limited systemic therapeutic options. Although expression of the PI3K pathway did not correlate with OS and survival after BCBM, PTEN- association with time to recurrence and OS (among patients with TNBC) is worthy of further study.     

Occurrence and outcome of de novo metastatic breast cancer by subtype in a large,diverse population

Purpose

To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression.

Methods

We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of Stage IV versus Stage I–III breast cancer; Cox proportional hazards regression was used to assess relative hazard (RH) of mortality.

Results

Five percent of invasive breast cancer was metastatic at diagnosis. Compared to patients with earlier stage disease, patients with de novo metastatic disease were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI 1.17–1.42; HR?/HER2+: OR 1.40, 95 %CI 1.25–1.57, vs. HR+/HER2?). Median survival improved over time, but varied substantially across race/ethnicity (Asians: 34 months; African Americans: 6 months), neighborhood socioeconomic status (SES) (highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45 months; triple negative: 12 months). In a multivariable model, triple negative (RH 2.85, 95 % CI 2.50–3.24) and HR?/HER2+ (RH 1.60, 95 % CI 1.37–1.87) had worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2? breast cancer.

Conclusions

De novo metastatic breast cancer was more likely to be HER2+. Among metastatic tumors, those that were HER2+ had better survival than other subtypes.

     

Risk of death from cardiovascular disease following breast cancer: a systematic review

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.

     

Demographic and clinico-pathological characteristics in patients with triple-negative and non-triple-negative breast cancer

We investigate retrospectively the demographic and clinico-pathological characteristics of patients with triple-negative breast cancer (TNBC) compared to those with non-TNBC. Patients with breast cancer diagnosed from 1981 to 2008 in our clinic were retrospectively analyzed. Patient demographics including survival data and tumor characteristics were obtained from charts. A total of 795 patients were assessed in the study, including 140 patients (17.6%) with TNBC and 655 patients (82.4%) with non-TNBC. Patients with non-TNBC were further classified into 3 groups according to hormone receptor (HR) and HER-2 status. Median age was 49 (range 38–60 years) and similar between patients with TNBC and non-TNBC. Patients with TNBC had an increased likelihood of a higher histological grade III compared with HR(+) HER-2(?) subgroup (P > 0.001) and lower stage compared with HR(+)/HER2(+) and HR(?)/HER2(+) subgroups (P < 0.001 and P = 0.002, respectively). In patients with TNBC, the disease-free survival (DFS) rate was 66% at 5 years. In subgroup analysis of non-TNBCs, 5-year-DFS rates of the patients in HR(+)/HER2(?), HR(+)/HER2(+) and HR(?)/HER2(+) subgroups were 59, 66, and 57%, respectively. There was no significant difference between the TNBC and non-TNBC subgroups (P = 0.238). In multivariate analysis, nodal involvement (RR = 2.8, 95% CI: 0.99–8.3, P = 0.052) and the presence of lymphovascular invasion (RR = 3.2, 95% CI: 1.1–9.2, P = 0.029) were significantly associated with increased recurrence risk in patients with TNBC. Although there are differences in patient and tumor features, patients with TNBC had similar clinical course with those with non-TNBC.     

Recent developments in the palliative treatment of breast cancer: ASCO 2013

Purpose

Highly selected abstracts from the ASCO meeting are reported.

Results and conclusions

Abstract #1040: Subgroup analysis of TURANDOT (first-line paclitaxel and bevacizumab (T + BEV) versus capecitabine and BEV) was presented; 130 patients had triple-negative disease. One-year overall survival of T + BEV-treated patients with triple-negative disease was 78 %. Thus, T + BEV may represent a preferred regimen. Abstract #514: Evidence for drug penetration of capecitabine and lapatinib was demonstrated in resected brain metastases from breast cancer. Patients scheduled for brain surgery received pre-operative therapy. Drug concentrations were detected in all lesions. Thus, capecitabine and lapatinib may penetrate the blood-brain barrier. Abstract #505: In BOLERO-3, everolimus (EVE) or placebo plus trastuzumab/vinorelbine were administered to trastuzumab-resistant, HER2-positive breast cancer after previous taxanes. In the EVE versus placebo group, median progression-free survival (PFS) was 7.0 versus 5.7 months, respectively. Thus, a positive effect of EVE was found. Abstract #555: Prognostic factors in HER2-negative breast cancer patients receiving first-line bevacizumab (BEV) plus non-anthracycline therapy were investigated. Negative factors were disease-free interval £ 24 months, liver metastases or ³ 2 involved organs, triple-negativity and adjuvant taxanes/anthracyclines, respectively. Thus, established prognostic factors were also confirmed in BEV-treated patients. Abstract #1049: Subgroup analyses of the phase-III trial of eribulin versus capecitabine in metastatic breast cancer pre-treated with anthracyclines/taxanes was carried out. Overall survival was predicted by non-visceral disease, > 2 organs involved, and PFS of < 6 months after last chemotherapy. Eribulin was superior in patients with > 2 metastatic sites, HER2-negative, ER-negative, and triple-negative disease, respectively. The latter patients may preferentially benefit from eribulin therapy.     

The prognostic contribution of clinical breast cancer subtype, age, and race among patients with breast cancer brain metastases

BACKGROUND:

Brain metastases (BM) arising from triple‐negative breast cancer (TNBC) portend a poor prognosis. TNBC is more common in premenopausal and African‐American (AA) patients; both of these characteristics also confer a poor prognosis. In a single‐institution cohort study, the authors attempted to determine whether the inferior outcome noted with TNBC brain metastases is more reflective of a higher risk population or the subtype itself.

METHODS:

The University of North Carolina Breast Cancer Database identified patients with BC brain metastases who were diagnosed between 1988 and 2008. BC subtype was assigned by immunohistochemistry: hormone receptor (HR) positive (+);(HR, estrogen receptor [ER]+ and/or progesterone receptor [PR]+)/human epidermal growth factor receptor 2 (HER2) negative (‐), HR+/HER2+, HR‐/HER2+, and TN (ER‐/PR‐/HER2‐). Survival and disease recurrence patterns were evaluated by subtype, patient age (<40 years vs ≥40 years), and race (AA vs non‐AA) using the Kaplan‐Meier method and Cox regression analysis.

RESULTS:

Among 119 patients with BC brain metastases, 33% were AA and 31% were aged <40 years. BC subtype was confirmed in 98 patients (30% with HR+/HER2‐, 21% with HR+/HER2+, 18% with HR‐/HER2+, and 31% with TNBC). Survival after BM was found to be impacted by subtype (P = .002), and was shortest for patients with TNBC (0.24 years; 95% confidence interval, 0.17 years‐0.48 years). There were no age‐specific (P = .84) or race‐specific (P = .09) differences in survival noted after brain metastases; stratification of BC subtypes by age and race revealed no difference (all, P > .1). The receipt of systemic therapy after BC brain metastases was found to be an important predictor of survival after BC brain metastases (hazard ratio, 0.29; P = .002) when adjusted for race, age, number of central nervous system lesions, and BC subtype.

CONCLUSIONS:

TNBC confers a high risk of death after brain metastases regardless of patient race and age, supporting the need for novel agents capable of controlling both intracranial and extracranial TNBC across all races and ages. Cancer 2011. © 2010 American Cancer Society.     

Patterns of relapse and metastatic spread in HER2-overexpressing breast cancer according to estrogen receptor status

Purpose

The primary aim of this study was to compare the relapse patterns of estrogen receptor (ER)-positive and ER-negative patients with HER2-overexpressing breast cancer. A secondary aim was to distinguish the preferential primary site of metastases in HER2-overexpressing breast cancer.

Methods

Out of 886 patients treated for metastatic breast cancer (MBC) between January 1995 and December 2006, 269 patients with HER2-positive tumors were identified. Of these, 198 patients with relapsed breast cancer following surgery were included in this study. Rates and patterns of relapse and metastatic spread in HER2+/ER+ and HER2+/ER? patients were analyzed. This analysis was evaluated by the validation patients’ cohort of our institute prospectively.

Results

Median relapse-free survival was longer in the HER2+/ER+ group than in the HER2+/ER? group (32.0 vs. 19.5 months, p = 0.0012). The peak of recurrence occurred at 12 months after surgery in the HER2+/ER? patients. The peak of relapse was later and the level was lower in the HER2+/ER+ patients (66 and 78 months following surgery) than in the HER2+/ER? patients (33 and 39 months following surgery, respectively). This result was reproduced by the validation cohort with great similarity. Young age [hazard ratio (HR) 1.59, p = 0.002], TNM stage 3 (HR 1.51, p = 0.005), and ER-negativity (HR 1.68, p < 0.0001) were identified as independent risk factors for relapse. Severe bone metastasis (HR 4.48, p = 0.028) and massive hepatic metastasis (HR 5.24, p = 0.043) were identified as independent risk factors for early relapse.

Conclusions

Our study shows that HER2-overexpressing breast cancer displays characteristic patterns of relapse and metastatic spread depending on ER status.     

Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in HER2-negative primary breast cancer

Background

Docetaxel plus cyclophosphamide (TC) has recently been established as a standard adjuvant chemotherapy regimen for HER2-negative (HER2?) operable breast cancer. However, the efficacy and tolerability of TC as neoadjuvant chemotherapy (NAC) remain unclear. We, therefore, conducted a prospective study to evaluate the efficacy of TC NAC in HER2? primary breast cancer.

Methods

Patients who were diagnosed with HER2?, N0–N1, invasive breast cancer between July 2011 and February 2014 and had tumors measuring 1–7 cm were eligible. The subtypes were classified using a core-needle or vacuum-assisted breast biopsy. The efficacy and safety of NAC comprising TC (75 mg/m² docetaxel and 600 mg/m² cyclophosphamide, four cycles every 3 weeks) were investigated in a prospective study in patients with HER2? breast cancer.

Results

Fifty-two patients were enrolled. Of these, 94.2 % (49/52) completed four cycles of TC. The overall pCR rate was 16.3 % (8/49). The pCR rates for patients with luminal A-like breast cancer [estrogen receptor-positive (ER+), Ki67 index of <20 %, and HER2?], luminal B-like breast cancer (ER+, Ki67 index of >20 %, and HER2?), and triple-negative breast cancer [ER-negative (ER?) and HER2?] were 0 % (0/12), 4.3 % (1/23), and 50.0 % (7/14), respectively. Almost all pCRs occurred in triple-negative breast cancer patients.

Conclusions

The pCR rate of TC NAC was not very high despite the high completion rate. TC NAC was effective against the triple-negative subtype, resulting in a higher pCR rate. Therefore, our results indicated that TC NAC showed limited efficacy in luminal subtype breast cancer with the exception of the triple-negative subtype.

     

Occurrence of breast cancer subtypes in adolescent and young adult women

Introduction

Breast cancers are increasingly recognized as heterogeneous based on expression of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2). Triple-negative tumors (ER^-/PR^-/HER2^-) have been reported to be more common among younger women, but occurrence of the spectrum of breast cancer subtypes in adolescent and young adult (AYA) women aged between 15 and 39 years is otherwise poorly understood.

Methods

Data regarding all 5,605 AYA breast cancers diagnosed in California during the period 2005 to 2009, including ER and PR status (referred to jointly as hormone receptor (HR) status) and HER2 status, was obtained from the population-based California Cancer Registry. Incidence rates were calculated by subtype (triple-negative; HR⁺/HER2^-; HR⁺/HER2⁺; HR^-/HER2⁺), and logistic regression was used to evaluate differences in subtype characteristics by age group.

Results

AYAs had higher proportions of HR⁺/HER2⁺, triple-negative and HR^-/HER2⁺ breast cancer subtypes and higher proportions of patients of non-White race/ethnicity than did older women. AYAs also were more likely to be diagnosed with stage III/IV disease and high-grade tumors than were older women. Rates of HR⁺/HER2^- and triple-negative subtypes in AYAs varied substantially by race/ethnicity.

Conclusions

The distribution of breast cancer subtypes among AYAs varies from that observed in older women, and varies further by race/ethnicity. Observed subtype distributions may explain the poorer breast cancer survival previously observed among AYAs.     

Clinicopathological features of early failure of neoadjuvant chemotherapy in locally advanced breast cancer

Purpose

Neoadjuvant chemotherapy (NAC) has been used widely in patients with locally advanced breast cancer (LABC). NAC has the added advantage of increasing breast conservation rates with similar disease-free and overall survival compared with adjuvant chemotherapy. A subset of patients receiving NAC experience early failure during the course of therapy or within a short period after breast surgery. There are no established predictors of early therapy failure in LABC patients who received NAC. This study was performed to identify patient groups that may not benefit from NAC.

Patients and methods

This study was a retrospective single-centre study. Patients with LABC (cT2-4N0-3) were recruited into this analysis from January 2005 to December 2011 at the Samsung Medical Center. The cohort included 397 patients. The clinicopathological characteristics and disease courses of the patients whose disease progressed within 1 year of receiving neoadjuvant chemotherapy were analysed.

Results

Thirty-eight of the 397 patients (9.6 %) exhibited progression within 1 year after receiving neoadjuvant chemotherapy. Seven of the 37 patients (18.9 %) with a known disease subtype, as assessed by IHC, were hormone receptor (HR)+ and HER2?. The number of HER2+ irrespective of HR status and triple-negative breast cancer (TNBC) patients was 13 (35.1 %) and 17 (45.9 %), respectively. Pathological complete remission was found in two patients (5.3 %, 2/38). The median overall survival period was 20.4 months (95 % CI 17.3–23.5) in patients with early failure and 69.1 months (95 % CI 52.7–85.4) in the late failure group (p < 0.001), with a median follow-up period of 35.7 months. The central nervous system (CNS) was the most common site of first distant metastasis (31.6 %, 12/38), and CNS failure was more common in patients with early failure compared with those with late failure (32.4 vs. 3.1 %, p = 0.000). HER2 positivity or TNBC and the presence of lymphovascular invasion were independent predictors of early failure.

Conclusions

A fraction of patients with LABC may not benefit from neoadjuvant chemotherapy. The results of our study suggest that early failure marks a high-risk group of patients who require innovative therapeutic approaches.     

Smoking and alcohol consumption in relation to risk of triple-negative breast cancer in a cohort of postmenopausal women

Purpose

Little is known about the risk factors for triple-negative breast cancer (TNBC), which has a worse prognosis compared to hormone receptor-positive breast cancer. We examined the association of smoking and alcohol intake with TNBC and estrogen receptor-positive (ER+) breast cancer.

Methods

Among 148,030 women enrolled in the Women??s Health Initiative, 300 TNBC cases and 2,479 ER+ cases were identified over a median of 8.0 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).

Results

Cigarette smoking was not associated with TNBC, whereas drinkers had reduced risk compared to never drinkers. In contrast, both exposures showed slight positive associations with ER+ breast cancer: for women with ??40 pack-years of smoking, the HR was 1.24, 95% CI 1.06?C1.44; for women consuming ??7 servings of alcohol per week, the HR was 1.26, 95% CI 1.06?C1.50. Intakes of wine and hard liquor were also significantly positively associated with ER+ breast cancer.

Conclusions

These findings from a large cohort of postmenopausal women suggest that smoking and alcohol consumption are not associated with increased risk of TNBC, but may be modestly associated with increased risk of ER+ breast cancer.     

Clinical subtypes and prognosis of pregnancy-associated breast cancer: results from the Korean Breast Cancer Society Registry database

Purpose

We analyzed the clinicopathologic characteristics and prognosis of pregnancy-associated breast cancer (PABC) according to clinical subtypes to better understand the characteristics of PABC.

Methods

A total of 83,792 female patients between the ages of 20 and 49 were enrolled in the Korean Breast Cancer Society Registry database from January 1, 1996 to December 31, 2015. ‘PABC’ is defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. Other patients were defined as ‘non-PABC’ patients.

Results

In non-PABC patients, luminal A subtype was the most common (50.2%). In PABC patients, TNBC was the most common (40.4%) subtype, while luminal A comprised 21.2% and HER2 subtype comprised 17.3%. There was a significant difference in overall survival (OS). In non-PABC patients, TNBC had the highest HR (HR 2.3, 95% CI 2.1–2.6). In PABC patients, the luminal B subtype (HR+ HER2-high Ki67) had the highest HR at 7.0 (95% CI 1.7–29.1). In multivariate analysis of OS by subtypes, PABC patients had significantly higher HR than non-PABC patients in the HER2 subtype (HR 2.0, 95% CI 1.1–3.7) and luminal B subtype (HR+ HER2-high Ki67) (HR 4.4, 95% CI 1.6–12.3).

Conclusion

PABC showed different biologic features than non-PABC. PABC had a particularly poor prognosis in the luminal B (HR+ HER2-highKi67) and HER2 subtypes. To improve the prognosis of PABC, treatment should be considered according to subtype. Development of drugs that can be used during pregnancy is needed.

     

Mortality risk from comorbidities independent of triple-negative breast cancer status: NCI-SEER-based cohort analysis

Purpose

A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients.

Methods

We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000–2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors.

Results

Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14–4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74–3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29–1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90–11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68–5.29).

Conclusions

comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.

     

Among triple-negative breast cancers, HER2(0) breast cancer shows a strong tendency to be basal-like compared with HER2(1+) breast cancer: preliminary results

Background

Diagnosis of triple-negative breast cancer (ER-negative, PgR-negative, HER2-negative; TNBC) is performed by means of immunohistological staining. HER2-negative includes HER2(0) and HER2(1+), based on differences in the staining intensity, but there have been no reports on comparison of these two types in TNBC. Accordingly, this study was designed to investigate the possible differences in the biological characteristics of HER2(0) breast cancer and HER2(1+) breast cancer in TNBC.

Methods

Tissue specimens from 89 TNBC patients were immunohistochemically stained for CK5/6, EGFR, p53, Ki67, E-cadherin, TOP2A and Bcl-2. The expressions of these markers and the clinicopathological findings were compared between the HER2(0) patient group and the HER2(1+) patient group. When either CK5/6 or EGFR was positive, the specimen was judged to be the basal-like phenotype of breast cancer.

Results

The percentages of CK5/6- and/or EGFR-positive specimens in the HER2(0) and HER2(1+) groups were 44.9 and 16.8%, respectively, showing that there was a significantly greater number of basal-like phenotype patients in the HER2(0) group (p?<?0.01). The percentage of E-cadherin-positive specimens in the HER2(0) group was 66.6%, which was significantly greater than the 40.0% recorded in the HER2(1+) group (p?<?0.05). The respective percentages of TOP2A-positive specimens in the HER2(0) and HER2(1+) groups were 55.0 and 30.0%, and the difference was statistically significant (p?<?0.05).

Conclusion

In TNBC, HER2(0) breast cancer showed a strong tendency to include more of the basal-like phenotype compared with HER2(1+) breast cancer. The staining results indicated the possibility that HER2(0) breast cancer and HER2(1+) breast cancer have different characteristics.     

Different prognosis of young breast cancer patients in their 20s and 30s depending on subtype: a nationwide study from the Korean Breast Cancer Society

Purpose

Numerous studies have demonstrated that breast cancer in young women (BCY) has unfavorable prognostic features and more unfavorable subtypes. However, few studies have evaluated the effect of subtype disparities on breast cancer prognosis by age, especially for BCY. We analyzed breast cancer mortality stratified by tumor subtype according to age among patients younger than 50 years.

Methods

Data from the Korean Breast Cancer Society Registry for patients diagnosed with invasive breast cancer when aged less than 50 years between 2003 and 2010 were reviewed retrospectively.

Results

We identified 30,793 patients with breast cancer who were eligible for analysis. Of these, 793 (2.6%) were aged 20–29 and 8926 (28.8%) were aged 30–39. Median follow-up duration was 84 months. Mean age was 42.4 years. Patients in their 20s were more likely to have cancer of advanced stage and higher nuclear grade, present with lymphovascular invasion, and have unfavorable subtypes. Patients in the 20s group showed worse prognosis. In multivariate analysis for overall survival (OS), the hazard ratio (HR) for patients in the 20s group was higher than that for the 30s and 40s groups, and patients with triple-negative breast cancer (TNBC) showed higher HR than patients with HER-2 or luminal subtype (all p < 0.0001). When stratified by subtype, luminal subtype showed significantly worse prognosis in the 20s group than the 30s and 40s groups, whereas HER-2 and TNBC subtypes showed no significant difference.

Conclusion

Patients in their 20s with breast cancer had unfavorable characteristics and worse prognosis than patients in their 30s and 40s. When stratified by tumor subtype, patients in their 20s with luminal subtype of breast cancer showed worse prognosis than older patients, whereas HER-2 and TNBC subtypes showed no significant differences.