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.

     

Adiposity,post-diagnosis weight change,and risk of cardiovascular events among early-stage breast cancer survivors

Purpose

We hypothesized different Overall Survival (OS) in metastatic breast cancer (MBC) after relapse vs de novo presentation.

Methods

We identified women in British Columbia with MBC diagnosed between 01/2001 and 12/2009. OS from MBC was calculated for relapsed vs de novo cohorts in 3 subgroups, based on hormone receptors (HR) and HER2 status. Age at MBC, disease-free interval (DFI), de novo vs relapsed, year of MBC diagnosis, and systemic treatment were entered into univariable and multivariable analyses.

Results

We identified 3645 pts with known HR of which 2796 had known HER2. Median follow-up was 91 months. Median OS was longer for de novo vs relapsed MBC: HR+/HER2- 34 versus 23 months (mos) (p < 0.0001), HR?/HER2- (TN) 11 versus 8 mos (p = 0.02), HER2+ 29 versus 15 mos (p < 0.0001). For TN disease, no variable independently discriminated a group with increased risk of death. For both the HR +/HER2- and the HER2 + groups, relapsed vs de novo status (HzR 1.4 [95% CI 1.2–1.5; p < 0.0001], and HzR 1.6 [95% CI 1.4–1.9; p < 0.0001], respectively) and age >50 (HzR 1.2 [95% CI 1.1–1.4; p = 0.001] and HzR 1.3 [95% CI 1.1–1.5; p = 0.01], respectively) were associated with increased risk of death on multivariable analysis.

Conclusion

These data provide information that may guide discussions about prognosis between physicians and patients with MBC. In addition, it highlights the importance of stratifying for initial stage at diagnosis in future MBC therapeutic trials.

     

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial

Purpose

Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer.

Methods

Postmenopausal women with HR+ , HER2? advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate.

Results

Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27–0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population.

Conclusions

Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2? de novo advanced breast cancer.

     

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.

     

A pilot study of cabergoline for the treatment of metastatic breast cancer

Purpose

The prolactin (PRL) receptor is over-expressed in breast cancer, and pre-clinical data indicate that it contributes to breast oncogenesis. Cabergoline is a potent dopamine receptor agonist of D2 receptors and has a direct inhibitory effect on pituitary PRL secretion.

Methods

A phase II study of cabergoline in patients with metastatic breast cancer was conducted. The primary end point of the study was to determine the clinical benefit rate (CBR) at 2 months. Eligible patients had tumors of any receptor status with no limit of prior lines of therapy. Measurable and unmeasurable diseases were allowed. Cabergoline 1 mg orally, twice weekly (1 cycle = 4 weeks) was given until disease progression or unacceptable toxicity. PRL receptor immunohistochemical staining was performed on available baseline tumor tissue; serial serum PRL levels were assessed.

Results

Twenty women were enrolled; 18 were evaluable for CBR. Tumor receptor status was distributed as follows: HR?any/HER2+ 2(10%), HR+/HER2? 18 (90%). The CBR was 33% (6/18), median progression free survival was 1.8 months, and median overall survival was 10.4 months. Two patients experienced disease control for over 12 months. Most common treatment-related adverse events were nausea (30%), fatigue (25%), and elevation in alkaline phosphatase (15%). Nine patients had baseline tissue for analysis; there was no association between baseline tumor PRL receptor expression and clinical benefit (p = 0.24). Change in serum PRL level and response were not correlated after 2 months of treatment (p = 0.64).

Conclusion

Cabergoline was well tolerated, and while the ORR was low, a small subset of patients experienced extended disease control.

     

The breast graded prognostic assessment is associated with the survival outcomes in breast cancer patients receiving whole brain re-irradiation

Introduction

Whole brain (WB) re-irradiation for breast cancer patients with progressive brain metastasis after first-course WB radiotherapy (WBRT) is controversial. In this study, we sought to investigate the association between the molecular sub-classifications and breast-specific Graded Prognostic Assessment (GPA, which includes the Karnofsky performance status, molecular subtypes, and age as its indices) and the outcomes of breast cancer patients who received WB re-irradiation.

Methods

Twenty-three breast cancer patients who received WB re-irradiation for relapsed and progressive intracranial lesions after first-course WBRT between 2004 and 2016 were retrospectively reviewed. Patients were divided according to the 4 molecular subtypes of luminal A/B (hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]?), luminal HER2 (HR+/HER2+), HER2 (HR?/HER2+), and triple negative (HR?/HER2?). The clinical and radiological responses and survival rates after WB re-irradiation were analyzed.

Results

At 1 month after WB re-irradiation, 13 of 23 patients (56.5%) exhibited disappearance or alleviation of neurological symptoms. The median survival time after WB re-irradiation was 2.93 months (95% confidence interval [CI], 1.79–4.08). After WB re-irradiation, patients with HER2-negative tumors had poorer median survival times than those with HER2-positive tumors (2.23 vs. 3.0 months, respectively; p?=?0.022). Furthermore, patients with high breast GPA scores (2.5–4.0, n?=?11) had longer median survivals than those with low-scores (0–2.0, n?=?12) after WB re-irradiation (4.37 vs. 1.57 months, respectively; p?<?0.005).

Conclusions

WB re-irradiation may be a feasible treatment option for certain breast cancer patients who develop brain metastatic lesions after first-course WBRT when these lesions are ineligible for radiosurgery or surgery.

     

Novel Agents for the Management of Endocrine Resistant Breast Cancer

Purpose of Review

Most women with hormone receptor (HR)-positive, HER2-negative (HR+/HER2?) breast cancer will ultimately develop endocrine-resistant disease, either primary or acquired. This review will discuss the proposed mechanisms underlying endocrine resistance and key advances in the treatment of endocrine-resistant breast cancer.

Recent Findings

Estrogen receptor 1 mutations (ESR1) occur in the majority of patients with HR+/HER2? metastatic breast cancer after prolonged exposure to aromatase inhibitors. Data from the SoFEA trial showed that patients had improved progression-free survival (PFS) after taking fulvestrant compared with exemestane. Fulvestrant is currently the only selective estrogen receptor degrader (SERD) available and development of oral novel SERDs with higher bioavailability and potency are currently being investigated.

Summary

Despite significant advances in the treatment of HR+/HER2? breast cancer over the past four decades, a significant proportion of patients do still develop endocrine resistance following optimal endocrine therapy. In this review, we aim to provide an overview of the different classes of novel agents currently being investigated to overcome endocrine resistance.

     

Benefits of using the cell block method to determine the discordance of the HR/HER2 expression in patients with metastatic breast cancer

Background

The discordance of the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expressions between primary cancer and metastatic lesions is an important issue when selecting the optimal treatments for patients with metastatic breast cancer. A rebiopsy for the metastatic cancer is recommended before selecting the treatment; however, it is not easy to take a tissue sample for all metastatic lesions. Fine needle aspiration cytology (FNA) for regional lymph nodes and aspiration for pleural effusions or ascites are less invasive procedures to obtain the necessary samples to examine the HR/HER2 expression. These cytologic materials are able to be stained as a tissue sample using the cell block method.

Patients

We examined the HR/HER2 expression of 20 patients with breast cancer (8 with synchronous metastases and 12 with metachronous metastases) using the cell block method. Among 8 patients with synchronous metastases, 7 patients with axillary lymph node (LN) metastasis were examined by fine needle aspiration (FNA), and one patient with pleural metastases was analyzed for the aspirated fluid. While in 12 patients with metachronous metastases, 7 patients were examined for their pleural effusion, 3 patients were examined for regional lymph node metastases, and 1 patient were examined for aspirated ascites. We compared the HR/HER expression between primary cancer and metastatic lesion in 17 patients (5 cases of 8 synchronous metastases, and all of 12 metachronous metastases).

Results

Discordance of HR was seen in 4 of 17 patients (24 %). Three cases with axillary LN metastasis (2 cases with synchronous metastases and one with metachronous metastasis) showed negative change of ER. Negative change of HER2 expression was seen in one patient with ascites caused by peritoneal dissemination.

Conclusions

Cytology materials are easily obtained by FNA for LN metastases and aspiration for malignant effusions and analyzed for HR/HER2 expression using cell block method. We should take advantage of cell block analysis to determine the discordance of the HR/HER2 expression to select the optimal treatment for metastatic breast cancer.

     

The yield of full <Emphasis Type="Italic">BRCA1</Emphasis>/<Emphasis Type="Italic">2</Emphasis> genotyping in Israeli high-risk breast/ovarian cancer patients who do not carry the predominant mutations

Purpose

Patients treated with trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) are living longer, but there is little information on their outcomes and treatment experience beyond the median survival from clinical trials and real-world observational studies. We aim to describe the real-world treatment patterns and overall survival (OS) for women surviving five or more years from initiation of trastuzumab for HER2+MBC.

Methods

This is a retrospective, whole-of-population cohort study of women initiating trastuzumab for HER2+MBC between 2001 and 2011, followed to 2016. We defined long-term survivors (LTS) as those patients surviving?≥?5 years from trastuzumab initiation. We used dispensing claims to describe timing of cancer treatments used by LTS and to estimate time on and off HER2-targeted therapies, and OS from trastuzumab initiation for HER2+MBC.

Results

Of 4177 women initiating trastuzumab for HER2+MBC, 1082 (26%) survived ≥?5 years. Median age for LTS was 54 years (IQR 46–63). At a median follow-up of 9.4 years, 36% of LTS died; their conditional probability of surviving an additional 5 years was 55%. Median time on trastuzumab and all HER2-targeted therapy was 58.9 months (27.6–88.1) and 69.1 months (35.6–124.5), respectively. 85% of LTS had a period off HER2 therapy, lasting a median of 30.4 months (8.2–NR).

Conclusions

LTS generally receive HER2-targeted therapies for periods of time longer than in clinical trials, but most LTS also had breaks in treatment. More research is needed to understand the effects of long-term treatment and to identify patients who may be able to safely discontinue HER2-targeted therapy.

     

Optimal vascular access strategies for patients receiving chemotherapy for early-stage breast cancer: a systematic review

Purpose

Prospective information regarding the tolerability and efficacy of endocrine therapy (ET) alone and in combination with targeted agents in older patients in the metastatic setting is limited. This review summarizes available trial data in this population.

Methods

We searched PubMed for Phase 2 or 3 trials with age-stratified patient cohorts (≥ 65 vs. < 65 years in most studies) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2?) advanced breast cancer treated with ET ± targeted agents.

Results

We identified 19 studies reporting 10 clinical trials. Efficacy was similar in age-stratified subsets. There was a reduced disease progression risk for ET + everolimus, palbociclib, or ribociclib versus ET alone. In the first-line setting, median progression-free survival (mPFS) in older patients was 8.5, 26.2 months, and not reached with letrozole + temsirolimus, palbociclib, and ribociclib, respectively, and in younger patients was 9.0, 18.8 months, and not reached, respectively. In the second-line setting, older patients had mPFS of 6.8 and 9.9 months with everolimus + exemestane and palbociclib + fulvestrant, respectively, and younger patients had mPFS of 8.1 and 9.5 months, respectively. Tolerability was worse for combination therapy versus monotherapy. No age-related differences in discontinuations were observed for CDK4/6 inhibitors, although a higher rate of treatment discontinuation was observed for patients ≥ 70 years receiving everolimus + exemestane. Adverse event rates were similar in age-stratified subsets.

Conclusions

ET + CDK4/6 or mTOR inhibitors are likely safe and effective in older patients with HR+, HER2? advanced breast cancer.

     

Tumor-infiltrating lymphocytes affect the efficacy of trastuzumab-based treatment in human epidermal growth factor receptor 2-positive breast cancer

Background

Immune responses play an important role in interrupting the progression of cancer cells. Tumor-infiltrating lymphocytes (TILs) are basic components of the immune system. In triple negative breast cancer, increased number of TILs is associated with excellent prognosis and response of chemotherapy. Here, we investigated whether TILs affect the efficacy of trastuzumab-based treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Methods

The study included 97 patients with stage I-III HER2-positive breast cancer. All patients were preoperatively treated with an anthracycline-based combination regimen, followed by taxane with trastuzumab from 2009 to 2013. Pathological complete response (pCR) was defined as the disappearance of invasive cancer cells regardless of the presence of in situ components. TILs were evaluated using pre-therapeutic needle biopsy specimens. We assessed the percentage of the breast stroma with TILs over the total intratumoral stroma and classified the specimens in three grades: TILs1+ < 30%, TILs2+ 30–50%, and TILs3+ > 50%.

Results

Overall, 80.4% of the specimens were TILs1+, 15.5% were TILs2+ and 4.1% were TILs3+. The pCR rate was 44.9% (35/78) in the TILs1+ cases, 80.0% (12/15) in the TILs2+ cases and 75.0% (3/4) in the TILs3+ cases. TILs were significantly associated with pCR (P = 0.0228). Multivariate analysis using TILs, hormone receptor (HR), nuclear grade (NG) and age indicated that TILs (OR 4.32, 95% CI 1.04–23.33, P = 0.0436) and HR (OR 8.76, 95% CI 3.30–25.44, P < 0.0001) were independent predictors for pCR.

Conclusion

TILs are associated with the efficacy of trastuzumab-based treatment in HER2-positive breast cancer.

     

Variation in guideline-concordant care for elderly patients with metastatic breast cancer in the United States

Purpose

Prior studies have identified shortcomings in the quality of care for early-stage breast cancer. Guidelines recommend systemic therapy for metastatic breast cancer (MBC), but few studies have examined guideline concordance for these patients.

Methods

We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify patients aged ≥ 66 diagnosed in 2010–2011 with de novo MBC who were continuously enrolled in fee-for-service Medicare. We described initial care (within 6 months of diagnosis) for hormone receptor (HR)-positive/human epidermal receptor-2 (HER2)-negative, HER2-positive, and triple-negative (TN) tumors. We identified factors independently associated with receiving no initial systemic therapy, and compared hospice and hospital utilization for treated versus untreated patients.

Results

Among 446 patients, 65% were HR-positive, 21% were HER2-positive, and 14% were TN. Most patients (76.9%) received initial systemic treatment. Among treated HR-positive patients, 15% received chemotherapy as initial treatment; among treated HER2-positive patients, 34% did not receive HER2-targeted initial therapy. Factors independently associated with receiving no initial systemic therapy included older age (OR_{age continuous/year} = 1.08, 95% CI 1.04–1.11), being not married (OR_{not married vs. married} = 2.87, 95% CI 1.42–5.81), and subtype (OR_{TN vs. HR+} = 4.95, 95% CI 2.53–9.71). Of patients who did not receive initial systemic therapy, 41.1% did not receive hospice services.

Conclusions

In this population-based MBC cohort, almost one quarter did not receive initial systemic therapy and a substantial proportion of treated patients did not receive guideline-concordant first-line therapy. Further research should explore underuse of chemotherapy and HER2-targeted therapies, investigate whether patterns of care are consistent with patient preferences, and identify opportunities to optimize hospice utilization for patients not receiving treatment.

     

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.

     

Contribution of clinical and socioeconomic factors to differences in breast cancer subtype and mortality between Hispanic and non-Hispanic white women

Purpose

To assess tumor subtype distribution and the relative contribution of clinical and sociodemographic factors on breast cancer survival between Hispanic and non-Hispanic whites (NHWs).

Methods

We analyzed data from the California Cancer Registry, which included 29,626 Hispanic and 99,862 NHW female invasive breast cancer cases diagnosed from 2004 to 2014. Logistic regression was used to assess ethnic differences in tumor subtype, and Cox proportional hazard modeling to assess differences in breast cancer survival.

Results

Hispanics compared to NHWs had higher odds of having triple-negative (OR = 1.29; 95% CI 1.23–1.35) and HER2-overexpressing tumors (OR = 1.19; 95% CI 1.14–1.25 [HR?] and OR = 1.39; 95% CI 1.31–1.48 [HR+]). In adjusted models, Hispanic women had a higher risk of breast cancer mortality than NHW women (mortality rate ratio [MRR] = 1.24; 95% CI 1.19–1.28). Clinical factors accounted for most of the mortality difference (MRR = 1.05; 95% CI 1.01–1.09); however, neighborhood socioeconomic status (SES) and health insurance together accounted for all of the mortality difference (MRR = 1.01; 95% CI 0.97–1.05).

Conclusions

Addressing SES disparities, including increasing access to health care, may be critical to overcoming poorer breast cancer outcomes in Hispanics.

     

Bright-field HER2 dual in situ hybridization (DISH) assay on breast cancer cell blocks: a comparative study with histological sections

Background

HER2 testing for samples from recurrent or metastatic disease is recommended by the 2013 update of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines and cytological analysis can be applied to several types of metastatic lesions. However, the practical method to assess the HER2 testing of breast cancer cytology specimens has yet to be resolved. Therefore, we conducted the bright-field HER2 dual in situ hybridization (DISH) assay on cell blocks (CBs) prepared from breast cancer cell samples as a validation study before clinical use.

Methods

CBs were prepared from tumor cell samples collected from 54 surgically excised breast tumors. The cells were fixed in 10 % buffered formalin for 16–28 h, and embedded in paraffin. The INFORM HER2/neu Dual ISH DNA Probe Cocktail was used for the DISH assay on the Ventana BenchMark ULTRA (Roche Diagnostics).

Results

Successful results were obtained in 51 of 54 CB specimens, and the results from the CB specimens were in agreement with those from the histological sections in 48 of the 51 cases (concordance rate, 94 %; kappa, 0.846). The intraclass correlation coefficient (ICC) between the CB and histological specimens in the continuous HER2/CEP17 signal count ratio was 0.89 (95 % CI 0.81–0.93), and the Pearson’s CC was 0.91 (95 % CI 0.85–0.94).

Conclusion

The HER2 DISH assay, utilizing 10 % buffered formalin-fixed CB, would be a reliable and ideal method to assess the HER2 gene status of breast cancer cytological specimens.

     

Durable complete response in HER2-positive breast cancer: a multicenter retrospective analysis

Purpose

Though advanced and metastatic epidermal growth factor receptor 2 (HER2)-positive disease is not curable, a small proportion of patients with HER2-positive metastatic breast cancer remain in prolonged complete remission with anti-HER2 treatment. We hypothesized that some cases of HER2-positive metastatic breast cancer may be curable. In this large, multicenter retrospective study, we aimed to assess the long-term outcomes for patients with a durable response to trastuzumab.

Methods

We retrospectively evaluated the data of patients diagnosed with HER2-positive metastatic breast cancer who received trastuzumab for more than 2 years as the first-line treatment. Patients diagnosed between April 1, 2001 and December 31, 2014 at 19 institutions in Japan were included in the analysis. From 124 potential subjects, 16 were excluded and 108 were evaluated.

Results

The median follow-up length was 7.7 years. Disease progression occurred in 44/108 (40.7%) patients and 13/108 (12%) patients died. The median progression-free survival was 11.2 years, and as more than 80% of patients were alive 10 years after metastatic breast cancer diagnosis. Of the 108 patients, 57 achieved a clinical complete response. Trastuzumab therapy was interrupted for 27 (47.4%) of these patients (based on the doctor’s recommendation for 19 patients, owing to adverse events for 4 patients, owing to unknown reasons for 3 patients, and at the request of 1 patient). Disease progression occurred in 4 of the 27 patients after the interruption of trastuzumab treatment. The median duration of trastuzumab therapy for all 27 patients was 5.1 years (0.9–9.3 years).

Conclusion

We found that some patients showed no evidence of disease after the interruption of trastuzumab therapy. Discontinuation of maintenance trastuzumab in this patient population after a limited time should be explored cautiously while awaiting a global collaborative effort for a randomized trial.

     

Comparison Between Prognostic Classifications in De Novo Metastatic Hormone Sensitive Prostate Cancer

Background

The CHAARTED and LATITUDE trials demonstrated improved outcomes with docetaxel or abiraterone plus androgen deprivation therapy in metastatic hormone sensitive prostate cancer (mHSPC) using two different prognostic scores.

Objective

The aim of our study was to assess the concordance between the two scores and if these retained their prognostic value exclusively in de novo mHSPC.

Patients and Methods

De novo mHSPC patients referring to our institution were retrospectively stratified according to the CHAARTED and LATITUDE classifications: high volume/high risk (HV/HR), low-volume/low-risk (LV/LR), and HVorHR (HV/LR and LV/HR). The Kaplan-Meier method and Cox proportional-hazard models were used to estimate hazard ratios for overall survival.

Results

The study population included 106 patients. Concordance between the CHAARTED and LATITUDE classifications was observed in 86.8% of cases (65.1% HV/HR, 21.7% LV/LR), while 13.2% of patients fulfill the criteria of only one of the two classifications (HVorHR). When analyzed independently, the CHAARTED and LATITUDE classifications maintained their prognostic value (mOS 28.2 months in HV versus 60.9 months in LV, p?=?0.006; 28.2 months in HR versus 40.6 months in LR, p?=?0.017). The LR/LV population showed significantly longer mOS compared to the HR/HV group (72.6 months versus 26.3 months; p?=?0.005), and to HVorHR patients (35.1 months; p?=?0.003). No difference in OS was observed between HV/HR and HVorHR patients. ECOG PS?≥?1 and patient age improved the prognostic value of the two classifications with multivariate analysis.

Conclusions

Our study showed a lack of complete concordance between the CHAARTED and LATITUDE classifications. The analysis confirmed the role of these prognostic scores to stratify de novo mHSPC patients in clinical practice.

     

Social well-being is associated with less pro-inflammatory and pro-metastatic leukocyte gene expression in women after surgery for breast cancer

Purpose

The data of 589 metastatic breast cancer (MBC) patients in a single institution were reviewed to determine the outcomes of patients with brain metastasis (BM) and assess the efficacy of BM screening.

Methods

The patients with BM among the 589 MBC patients who underwent treatment at Shizuoka Cancer Center (Shizuoka, Japan) from 09/2002 to 03/2014 were retrospectively analyzed.

Results

During the study period, BM developed in 187 (31.7%) patients. The tumor subtypes were as follows: luminal (hormone receptor [HR]+, HER2?), 44.9%; luminal-HER2 (HR+, HER2+), 14.9%; HER2 (HR?, HER2+), 21.3%; and triple-negative (TN), 16.0%. BM was detected in 48.6% of the patients by screening MRI. While 137 of 187 patients underwent local therapy, whole-brain irradiation was the most frequently applied therapy (63.5%). The median overall survival from the diagnosis of BM was as follows: luminal, 7.0 months (M); luminal-HER2, 13.3 M; HER2, 17.7 M; TN, 4.2 M. The HER2 status (hazard ratio [HR]: 0.58, 95% confidence interval [CI] 0.38–0.88) and nonprogressive extracranial lesion(s) (HR: 0.45, 95% CI 0.29–0.71) were identified as prognostic factors in a multivariate analysis. When limited to HER2-overexpressed MBC patients, the multivariate analysis revealed that non-progressive extracranial lesion(s) (HR: 0.20, 95% CI 0.088–0.47) and stereotactic irradiation (STI) as an initial treatment (HR: 0.18, 95% CI 0.061–0.56) were prognostic factors.

Conclusions

Our retrospective review showed that early detection of BM by screening MRI, followed by STI, improved the prognosis of HER2-overexpressed MBC patients with BM. A further prospective randomized study is needed to confirm our findings.

     

Clinicopathological predictive factors for ipsilateral and contralateral events following initial surgery to treat ductal carcinoma in situ

Background

Ipsilateral breast tumor recurrence (IBTR) after partial breast resection and contralateral breast tumor recurrence (CBTR) have been shown to occur relatively frequently in patients with ductal carcinoma in situ (DCIS). However, there is only limited data from Japanese institutes to support this.

Methods

Of 301 consecutive DCIS patients, 179 patients underwent a mastectomy, and the other 122 underwent partial resection in the National Cancer Center Hospital, Tokyo, with a median follow-up period of 2,106 days. We reviewed clinicopathological parameters including age, menopausal status, body mass index, family history (FH) of breast cancer, tumor size, histological subtype, nuclear grade (NG), hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, treatment, and the surgical margin status of partially resected specimens. The risk associated with each of these parameters for IBTR in 122 patients who underwent partial resections, and for CBTR in a total of 301 patients were calculated using Cox proportional hazard general linear models.

Results

Of the 122 patients who underwent partial breast resection, IBTR occurred in 7 (5.7 %). The risk of IBTR was higher or tended to be higher in younger patients or those with lower NG tumors, but did not change significantly with respect to margin status or irradiation. Amongst the entire cohort of 301 patients, CBTR occurred in 18 cases (6.0 %). CBTR occurred significantly more frequently in patients with a FH of breast cancer and with HR+/HER2? subtype tumors by univariate analyses, and tumor subtype was an independent risk factor for CBTR by multivariate analysis.

Conclusions

The local recurrence rate was low following partial resection of DCIS. Younger age was a risk factor for IBTR, whereas the HR+/HER2? tumor subtype and a FH of breast cancer were risk factors for CBTR.

     

First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2− advanced breast cancer: Tumor response and pain reduction in the phase 3 MONALEESA-2 trial

Purpose

The phase 3 MONALEESA-2 study demonstrated that addition of ribociclib (RIB) to letrozole (LET) significantly improved progression-free survival (PFS) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2?) advanced breast cancer (ABC). Here, we evaluated duration of response (DoR), tumor shrinkage, PFS by treatment-free interval (TFI), and health-related quality of life (HRQoL).

Methods

Postmenopausal women (N = 668) with HR+ , HER2? ABC and no prior systemic therapy for ABC were randomized to RIB (600 mg/day; 3 weeks on/1 week off) plus LET (2.5 mg/day; continuous) or placebo (PBO) plus LET. Primary end point was PFS; HRQoL was the secondary end point; DoR was exploratory end point and PFS by TFI was post hoc analysis.

Results

Of 501 pts with measurable disease and confirmed complete or partial response, median DoR was 26.7 months (95% CI, 24.0–NR) in the RIB arm versus 18.6 months (95% CI, 14.8–23.1) in the PBO arm. At 8 weeks, more pts in the RIB arm (32%) versus the PBO arm (17%) experienced best percentage change ≥ 60%. The average pain reduction was greater in the RIB arm (26%) versus the PBO arm (15%). PFS benefit was seen with RIB vs PBO, irrespective of TFI.

Conclusion

RIB plus LET versus PBO plus LET is associated with earlier and more durable tumor response, greater degree of tumor shrinkage and pain reduction, and PFS benefit irrespective of TFI. These data further support RIB plus LET as a first-line treatment option for postmenopausal women with HR+ , HER2? ABC.