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.

     

Clinicopathological and prognostic significance of Ki-67 immunohistochemical expression of distant metastatic lesions in patients with metastatic breast cancer

Background

Surgical biopsy of metastatic lesions followed by pathological confirmation for the investigation of biomarkers is occasionally proposed as an effective strategy in the treatment of metastatic breast cancer. However, few reports have examined Ki-67 immunohistochemical expression in distant metastatic lesions of breast cancer patients. This study aimed to investigate the clinicopathological significance of subtypes and Ki-67 immunohistochemical expression in metastatic breast cancer lesions.

Methods

We retrospectively studied surgical specimens of primary breast cancer tumors and their corresponding metastatic lesions from patients (n = 68) who underwent surgery for primary breast cancer tumors between December 1977 and March 2013. Tissue microarrays were constructed using primary and metastatic lesions, and were stained with antibodies against estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. We also examined the clinicopathological characteristics and outcome measures of patients with metastatic breast cancer using primary and paired metastatic lesions.

Results

Compared with the primary lesions, there was no significant difference in subtypes in the metastatic lesions according to metastatic sites. Metastatic lesions of the brain, viscera, and bone exhibited slightly higher levels of Ki-67 immunohistochemical expression compared with primary lesions. A Cox proportional hazards model using multivariate analysis demonstrated that high Ki-67 immunohistochemical expression in distant metastatic lesions was associated with poorer overall survival outcomes after biopsy of recurrence lesion (hazard ratio 2.307; 95% confidence interval 1.207–4.407, P = 0.011).

Conclusions

High Ki-67 immunohistochemical expression levels in distant metastatic lesions were independently associated with poorer overall survival outcomes after biopsy of recurrence lesion in breast cancer patients.

     

Adjuvant capecitabine plus oxaliplatin after D2 gastrectomy in Japanese patients with gastric cancer: a phase II study

Background

Adjuvant chemotherapy with XELOX (capecitabine plus oxaliplatin) has been shown to be beneficial following resection of gastric cancer in South Korean, Chinese, and Taiwanese patients. This phase II study (J-CLASSIC-PII) was undertaken to evaluate the feasibility of XELOX in Japanese patients with resected gastric cancer.

Methods

Patients with stage II or III gastric cancer who underwent curative D2 gastrectomy received adjuvant XELOX (eight 3-week cycles of oral capecitabine, 1000 mg/m² twice daily on days 1–14, plus intravenous oxaliplatin 130 mg/m² on day 1). The primary endpoint was dose intensity. Secondary endpoints were safety, proportion of patients completing treatment, and 1-year disease-free survival (DFS) rate.

Results

One hundred patients were enrolled, 76 of whom completed the study as planned. The mean dose intensity was 67.2 % (95 % CI, 61.9–72.5 %) for capecitabine and 73.4 % (95 % CI, 68.4–78.4 %) for oxaliplatin, which were higher than the predefined age-adjusted threshold values of 63.4 % and 69.4 %, respectively, and the study therefore met its primary endpoint. The 1-year DFS rate was 86 % (95 % CI, 77–91 %). No new safety signals were identified.

Conclusions

The feasibility of adjuvant XELOX in Japanese patients with resected gastric cancer is similar to that observed in South Korean, Chinese, and Taiwanese patients in the Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer (CLASSIC) study. Based on findings from this study and the CLASSIC study, the XELOX regimen can be considered an adjuvant treatment option for Japanese gastric cancer patients who have undergone curative resection.

     

Fulvestrant 500 mg in postmenopausal patients with metastatic breast cancer: the initial clinical experience

Background

Fulvestrant 500 mg is currently approved for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer after failure of prior endocrine therapies.

Methods

A total of 117 postmenopausal women with metastatic breast cancer, who experienced progression after previous endocrine therapies, were treated with fulvestrant 500 mg between January 2012 and June 2014. Clinical response, time to progression (TTP) and adverse events were investigated.

Results

Ninety-nine patients had recurrent breast cancer and 18 patients had stage IV disease. Patients had received a median of two endocrine therapies and a median of two chemotherapies, prior to fulvestrant. There were 10 patients with partial response, 39 patients with long stable disease, 18 patients with stable disease, and 50 patients with progressive disease, so that the objective response rate was 8.5 %, with a clinical benefit rate of 41.9 %. The median TTP was 6.1 months. The absence of liver metastases, a small number of previous chemotherapies, and the longer duration of first-line endocrine therapy were positively correlated with TTP in univariate analysis. In multivariate analysis, a significant association was observed between TTP and duration of first-line endocrine therapy. Serious adverse events were observed in one patient with pulmonary embolism and in one patient with psychiatric symptoms.

Conclusions

Fulvestrant 500 mg is an effective and well-tolerated treatment for postmenopausal women with metastatic breast cancer that had progressed after prior endocrine therapies. Patients with acquired resistance to endocrine therapies might be good candidates for fulvestrant therapy regardless of the number of prior endocrine treatments.

     

A phase II,multicenter, single-arm study of tri-weekly low-dose nanoparticle albumin-bound paclitaxel chemotherapy for patients with metastatic or recurrent breast cancer

Background

Nanoparticle albumin-bound (nab)-paclitaxel is a solvent-free formulation of paclitaxel that is bound to albumin and has demonstrated improved progression free survival in previous studies of breast cancer. However, it is difficult to treat Japanese patients with metastatic or recurrent breast cancer with the recommended dose of 260 mg/m² of (nab)-paclitaxel for more than six cycles due to the occurrence of adverse events. To evaluate the treatment continuity and safety of low-dose nab-paclitaxel, we conducted a phase II study of nab-paclitaxel in patients with metastatic or recurrent breast cancer who had received up to one prior chemotherapy.

Patients and methods

Treatment included low doses of 180 mg/m² nab-paclitaxel that were administered on day 1 of each 3-week cycle to 35 patients. The primary endpoint was the completion rate of six cycles of treatment.

Results

A total of 35 eligible patients were enrolled and received a median of eight (range 2–24) cycles of low-dose nab-paclitaxel therapy. The completion rate of six cycles of treatment was 66%. ORR and clinical benefit rate was 23 and 71%, respectively. Median PFS was 6.5 months and median OS was 44 months. Adverse events were relatively mild. Commonly observed grade 3/4 adverse events were neutropenia (46%), leukopenia (9%), and hypertension (3%). No grade 3-4 peripheral sensory neuropathy occurred.

Conclusion

Treatment with a low dose of nab-paclitaxel once every 3 weeks was tolerable and of acceptable safety and might be beneficial for patients with metastatic or recurrent breast cancer.

     

Reoperations after primary breast conserving surgery in women with invasive breast cancer in Catalonia,Spain: a retrospective study

Background

Although complete tumor resection is accepted as the best means to reduce recurrence, reoperations after lumpectomy are a common problem in breast cancer. The aim of this study was to assess the reoperation rates after primary breast conserving surgery in invasive breast cancer cases diagnosed in Catalonia, Spain, between 2005 and 2011 and to identify variations based on patient and tumour characteristics.

Methods

Women with invasive incident breast cancer identified from the Patient’s Hospital Discharge Database [174.0–174.9 codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as the primary diagnosis] and receiving primary breast conserving surgery were included in the study and were followed up to 3 and 12 months by collecting information about repeat breast cancer surgery.

Results

Reoperation rates after primary breast conserving surgery decreased from 13.0 % in 2005 to 11.7 % in 2011 at 3 months and from 14.2 % in 2005 to 12.9 % in 2011 at 12 months’ follow-up. While breast conservation reoperations saw a slight, non-significant increase in the same period (from 5.7 to 7.3 % at 3 months, and from 6.0 to 7.5 % at 12 months), there was a significant decrease in radical reoperation (from 7.3 to 4.4 % at 3 months and from 8.2 to 5.4 % at 12 months). Overall, additional breast surgeries decreased among younger women.

Conclusions

Despite the rise of breast conserving surgery, reoperation rates following initial lumpectomy in Catalonia decreased by 10 % at 3 and 12 months’ follow-up, remaining low and almost unchanged. Ultimately, there was also a significant decrease in mastectomies.

     

Preoperative diagnosis of sentinel lymph node (SLN) metastasis using 3D CT lymphography (CTLG)

Background

Sentinel lymph node biopsy (SLNB) became a standard procedure for patients with early breast cancer, however, an indication of SLN navigation to metastatic disease may lead to misdiagnosis for staging. Preoperative CTLG with a water-soluble iodinated contrast medium visualizes the correct primary SLNs and its afferent lymphatic channels surrounding detailed anatomy, therefore it can predict LN metastasis by visualizing the lymph vessel obstruction or stain defect of the SLN by tumor. The current study presents the value of CTLG for preoperative prediction for SLN status.

Methods

A total of 228 patients with Tis-T2 breast cancer who did not receive primary chemotherapy were studied. SLN metastasis was diagnosed according to the following staining patterns of SLNs and afferent lymphatic vessels: stain defect of SLN, obstruction, stagnation, dilation, and detour of the lymphatic vessels by tumor occupation. The diagnosis was compared with the pathological results to evaluate the accuracy of prediction for SLN metastasis using CTLG.

Results

Twenty-seven of 228 patients had metastatic SLN pathologically. Twenty-five of these were diagnosed as metastatic preoperatively. The accuracy for metastatic diagnosis using CTLG was 89.0 %, sensitivity was 92.6 %, and specificity was 88.6 %. The positive predictive value was 52.1 % and negative predictive value was 98.8 %.

Conclusion

CTLG can select the candidate with truly node negative cases in early breast cancer patients, because it predicts lymph node metastasis preoperatively from natural status of the lymphographic image. It also might omit the SLN biopsy itself.

     

Correlation of FANCM expression with clinical factors in luminal B breast cancer

Background

The genotype of Fanconi Anemia complementation group M (FANCM) was previously found to be associated with breast cancer risk in several populations. Here, we studied the expression of FANCM and its correlation with clinical characteristics in Chinese patients with breast cancer.

Methods

We performed an immunohistochemical study of FANCM protein in clinical breast cancer tissues from 310 patients along with 44 adjacent tissues.

Results

FANCM protein level is lower in triple-negative breast cancer tissues than in other subtypes (P = 0.008). In addition, high FANCM expression correlated with pathology type IDC (P = 0.040), estrogen receptor positive (P < 0.001), progesterone receptor positive (P = 0.001), and low Ki-67 status (P = 0.003). Multivariate analysis revealed that FANCM status was an independent prognostic factor for overall survival (P = 0.017) in luminal B breast cancer.

Conclusions

FANCM levels are significantly associated with different subtypes of human breast cancer. Specifically, FANCM could play a role in the progression of luminal B breast cancer.

     

Taste and smell perception and quality of life during and after systemic therapy for breast cancer

Purpose

The purpose of the study was to assess self-reported taste and smell perception after chemotherapy in breast cancer patients compared with women without cancer, and to assess whether taste and smell perception is associated with quality of life after the end of chemotherapy.

Methods

We included 135 newly diagnosed breast cancer patients who completed chemotherapy and 114 women without cancer. Questionnaires on taste, smell, and quality of life were completed shortly after and 6 months after chemotherapy (patients) or at two moments with 6 months’ time window in between (comparisons).

Results

Self-reported taste and smell perception were significantly lower in patients shortly after chemotherapy compared to the comparison group. Most patients recovered 6 months after chemotherapy, although patients who were still receiving trastuzumab then reported a lower taste and smell perception compared to patients who were not. A lower self-reported taste and smell were statistically significantly associated with a worse quality of life, social, emotional, and role functioning shortly after chemotherapy. Six months after chemotherapy, taste and smell were statistically significantly associated with quality of life, social and role functioning, but only in patients receiving trastuzumab.

Conclusions

Most taste and smell alterations recovered within 6 months after the end of chemotherapy for breast cancer, but not for patients receiving trastuzumab. These results highlight the importance of monitoring taste and smell alterations during and after treatment with chemotherapy and trastuzumab, as they may impact quality of life.

     

Preventing weight gain in African American breast cancer survivors using smart scales and activity trackers: a randomized controlled pilot study

Purpose

This study evaluated the feasibility and preliminary efficacy of two 6-month, self-regulation interventions that focused on daily self-weighing (DSW) and used objective monitoring and tailored feedback about weight (±activity), to prevent weight gain among African American breast cancer survivors.

Methods

Participants (n = 35) were randomized to an intervention + activity monitoring (INT+), intervention (INT), or control (CON) group. Interventions included a wireless scale (±activity tracker) that transmitted objective data to a mobile app/website, emailed lessons, and tailored feedback based on objective weight (±activity data). Participants completed in-person and online assessments at baseline, 3 months, and 6 months.

Results

Ninety-four percent of participants completed assessments at 3 months, and 97 % at 6 months. Median (IQR) weight change after 6 months was ?0.9 % (?4.4–0.1) in the INT+ (p = 0.075; p = 0.067 vs. CON) and ?0.2 % (?4.2–1.3) in the INT groups (p = 0.463; p = 0.357 vs. CON), versus a 0.2 % (?0.7–1.7) gain in the CON group. The proportion of INT+, INT, and CON participants that were at or below baseline weight was 72.7, 53.8, and 45.5 %, respectively (effect sizes d = 0.64, d = 0.18). Most INT+ participants weighed and wore trackers ≥5 days/week (INT+, 81.9 % vs. INT, 38.5 % vs. CON, 0 %; p < 0.0005; INT+, 72.7 %). Both intervention groups perceived DSW as positive, and 100 % would recommend the program to other breast cancer survivors.

Conclusion

An intervention focused on DSW as a self-monitoring strategy shows promise for preventing weight gain in breast cancer survivors.

Implications for cancer survivors

Daily self-monitoring of weight and activity may be a feasible and accessible approach to promote weight gain prevention in breast cancer survivors.

Clinical trial registration

ClinicalTrials.gov, NCT02030353

     

Economic and disease burden of breast cancer associated with suboptimal breastfeeding practices in Mexico

Purpose

Exclusive breastfeeding and longer breastfeeding reduce women’s breast cancer risk but Mexico has one of the lowest breastfeeding rates worldwide. We estimated the lifetime economic and disease burden of breast cancer in Mexico if 95% of parous women breastfeed each child exclusively for 6 months and continue breastfeeding for over a year.

Methods

We used a static microsimulation model with a cost-of-illness approach to simulate a cohort of Mexican women. We estimated breast cancer incidence, premature mortality, disability-adjusted life years (DALYs), medical costs, and income losses due to breast cancer and extrapolated the results to 1.116 million Mexican women of age 15 in 2012. Costs were expressed in 2015 US dollars and discounted at a 3% annual rate.

Results

We estimated that 2,186 premature deaths (95% CI 2,123–2,248), 9,936 breast cancer cases (95% CI 9,651–10,220), 45,109 DALYs (95% CI 43,000–47,217), and $245 million USD (95% CI 234–256) in medical costs and income losses owing to breast cancer could be saved over a cohort’s lifetime. Medical costs account for 80% of the economic burden; income losses and opportunity costs for caregivers account for 15 and 5%, respectively.

Conclusions

In Mexico, the burden of breast cancer due to suboptimal breastfeeding in women is high in terms of morbidity, premature mortality, and the economic costs for the health sector and society.

     

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice

Introduction

This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data.

Materials and methods

Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile.

Results

A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2? patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%).

Conclusions

Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

     

Routine treatment and outcome of breast cancer in younger versus elderly patients: results from the SENORA project of the prospective German TMK cohort study

Purpose

There is an ongoing discussion about ‘undertreatment’ of breast cancer in elderly patients. Due to low accrual into clinical trials, level 1 evidence is scarce. We report prospective data of elderly patients with breast cancer treated by medical oncologists in Germany.

Methods

The SENORA project within the prospective cohort study TMK (Tumour Registry Breast Cancer) was conducted in 82 centres from 2007–2015. Among 2316 patients, half were enrolled with curative and half with palliative treatment intention. Overall, 478 patients (21%) were aged ≥ 70.

Results

In the adjuvant setting, elderly patients aged ≥ 70 had more advanced tumour stages at diagnosis and a higher prevalence of comorbidities than younger patients. Elderly patients received adjuvant chemotherapy less frequently, yet the 3-year disease-free survival was similar (86% vs. 88%). In the palliative setting, elderly patients more frequently received endocrine therapy and less frequently chemotherapy. Their median overall survival [24.9 months, 95% CI (confidence interval) 20.0–30.2] was significantly shorter than that of younger patients (39.7 months, 95% CI 34.9–44.2). A Cox proportional hazards model showed a significantly increased risk of mortality for: age ≥ 70 at start of therapy, negative HR- or HER2-status, higher number of metastatic sites, more comorbidities and high tumour grading at diagnosis.

Conclusions

Our results shed light on the routine treatment of elderly patients with breast cancer. A regression model demonstrated that age is but one of various prognostic factors determining the shorter overall survival of elderly patients.

     

Adenoid cystic carcinoma of the breast, 20 years of experience in a single center with review of literature

Background

Adenoid cystic carcinoma (ACC) of the breast is a rare type of breast cancer, which presents inconsistencies in the optimal management strategy.

Methods

A retrospective review of prospectively collected data, spanning the last 20 years, was performed using the cancer registry database at our institution.

Results

Six patients were diagnosed with ACC of the breast, out of 5,813 total patients diagnosed with breast cancer (0.1%). Our identified patients had a median age of 66, all with the early stage cancer (Stage I/II). The average size of the breast lesion was 1.62 cm, and nodal status was negative for all cases. All patients had resection as primary therapy (partial or total mastectomy), with one patient also undergoing external beam radiation and tamoxifen hormonal therapy. Median follow-up was 85 months, with all patients being disease-free at last follow-up.

Conclusions

ACC of the breast has an indolent course, despite triple negative status. Our study suggests that radiation may not be warranted and confirms the rarity of axillary node metastases, indicating that sentinel node excision may also not be necessary. Ultimately, the hope is that our findings along with the reviewed literature will aid in determining the most appropriate options for management of ACC of the breast.

     

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.

     

Perometry versus simulated circumferential tape measurement for the detection of breast cancer-related lymphedema

Purpose

Therapeutic exploitation of angiogenesis in breast cancer has been limited by the lack of reliable biomarkers. Circulating small-sized endothelial microparticles (sEMP) are likely to play a significant role as messengers of angiogenesis. Higher levels of EMP have been observed in cancer patients, but their prognostic value in breast cancer is unknown. Our aim was to determine the value of circulating sEMP as a marker of response to chemotherapy in breast cancer.

Methods

We included patients with breast cancer treated with neoadjuvant or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+) were quantified using a flow cytometer approach specifically designed for analysis of small-sized particles (0.1–0.5 μm). Small-sized EMP response was defined as a post-treatment decrease of sEMP larger than the median decrease of sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were determined with ELISA.

Results

Forty-four breast cancer patients were included (19 with metastatic and 25 with locally advanced disease). Median levels of sEMP decreased after chemotherapy (P = 0.005). Response to chemotherapy showed a non-significant trend to associate with sEMP response (P = 0.056). A sEMP response was observed in 51% of patients and was associated with better overall survival (HR 0.18; 95% CI 0.04–0.87; P = 0.02) and progression free survival (HR 0.30; 95% CI 0.09–0.99; P = 0.04) in the group of women with metastatic disease. Post-chemotherapy decrease of VEGFA levels was not associated with breast cancer prognosis.

Conclusions

Our results did not support sEMP as a marker of response to chemotherapy. However, our exploratory analysis suggests that in patients with metastatic breast cancer, the decrease of sEMP levels after chemotherapy is associated with better overall and disease free survival and might be superior to VEGFA levels as an angiogenesis-related prognostic marker.

     

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.

     

Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women’s Health Across the Nation

Purpose

Two case–control studies reported a 50 % decreased breast cancer risk among women who experienced menopausal vasomotor symptoms (VMS), but one cohort study found no association. VMS may be triggered by declining estrogen levels during menopause, whereas elevated estrogen levels have been associated with increased breast cancer risk. VMS may thus be indicative of lower susceptibility to breast cancer.

Methods

We evaluated this relationship in the longitudinal Study of Women’s Health Across the Nation (SWAN), using discrete survival analysis of approximately annual data on VMS and self-reported breast cancer occurrences for up to 13 years of follow-up in 3,098 women who were pre- or early perimenopausal at enrollment.

Results

Over an average 11.4 years of follow-up, 129 incident breast cancer cases were self-reported, and approximately 50 % of participants experienced VMS. Symptomatic women had a reduced risk of breast cancer compared to non-symptomatic women (adjusted HR 0.63, 95 % CI 0.39, 1.00). The association was stronger in the subgroup of women who fully transitioned to postmenopause during follow-up (n = 67 cases, adjusted HR 0.45, 95 % CI 0.26, 0.77).

Conclusion

VMS appeared to be a marker of reduced breast cancer risk. Future research is needed to understand the biology underlying this relationship.

     

Changing patterns of microcalcification on screening mammography for prediction of breast cancer

Background

The presence of microcalcification on mammography is one of the earliest signs in breast cancer detection. However, it is difficult to distinguish malignant calcifications from benign calcifications. The aim of this study is to evaluate correlation between changing patterns of microcalcification on screening mammography and malignant breast lesions.

Methods

Medical records and diagnostic images of 67 women who had previously undergone at least two digital mammograms at least 6 months apart and underwent mammography-guided needle localization and surgical excision between 2011 and 2013 were retrospectively reviewed and analyzed.

Results

Breast cancer was detected in the surgical specimens of 20 patients (29.9 %). Annual change of extent of microcalcification on mammography showed statistically significant correlation with pathologic outcome (P = 0.023). The changing pattern of new appearance or increased extent of microcalcification on mammography had positive predictive value of 54.8 % for breast cancer, and it was a statistically significant predictor for breast cancer (P = 0.012). Shape or number change of microcalcification without increased extent had less accurate predictive value for breast cancer, particularly in women younger than 50 years (P < 0.001).

Conclusions

This study showed that the pattern of increased extent of microcalcification on screening mammography was a significant predictor for breast cancer. We suggest that mammography-guided needle localization and surgical excision should be considered when increased extent of microcalcification is observed on screening mammography and closed follow-up without pathologic confirmation can be permitted if absence of extension of microcalcification was confirmed in women younger than 50 years.