Postpartum diagnosis demonstrates a high risk for metastasis and merits an expanded definition of pregnancy-associated breast cancer

Previous studies report conflicting data on outcomes of pregnancy-associated breast cancer (PABC). Our aim was to examine the effect of a postpartum diagnosis on maternal prognosis in a young women’s breast cancer cohort. We conducted a retrospective cohort study of women age ≤45 years, diagnosed with breast cancer (n = 619) during 1981–2011 at the University of Colorado Hospital and The Shaw Cancer Center in Edwards, CO. Breast cancer cases were grouped according to time between giving birth and diagnosis: nulliparous (n = 125), pregnant (n = 24), < 5 years postpartum (n = 136), >5—<10 postpartum (n = 130), and ≥10 years postpartum (n = 147), to examine the clinicopathologic features and the risk of distance recurrence and death. Cases diagnosed after pregnancy, but within five-years postpartum, had an approximate three fold increased risk of distant recurrence (HR 2.80, 95 % CI: 1.12–6.57) and death (HR 2.65, 95 % CI: 1.09–6.42) compared to nulliparous cases. Postpartum cases diagnosed within five years of last childbirth demonstrated a higher five-year distant recurrence probability (31.1 %) and a markedly lower five-year overall survival probability (65.8 %) compared to nulliparous cases (14.8 and 98.0 %, respectively). A diagnosis of breast cancer during the first five-years postpartum confers poorer maternal prognoses after adjustment for biologic subtype, stage, and year of diagnosis. We propose that the definition of PABC should include cases diagnosed up to at least five-years postpartum to better delineate the increased risk imparted by a postpartum diagnosis. Based on emerging preclinical and epidemiologic data, we propose that pregnant and postpartum cases be researched as distinct subsets of PABC to clarify the risk imparted by pregnancy and the events subsequent to pregnancy, such as breast involution, on breast cancer. Further, we highlight the importance of postpartum breast cancer as an area for further research to reduce the increased metastatic potential and mortality of PABC.     

Variation in the Use of Boost Irradiation in Breast-Conserving Therapy in the Netherlands: The Effect of a National Guideline and Cofounding Factors

Aims

To determine the variation in radiation therapy boost use in a nationwide study following adjustment of a national guideline in 2011, as well as to address the relationship to patient, tumour and radiation therapy institutional factors.

A study of ductal versus non-ductal invasive breast carcinomas in older women: long-term clinical outcome and comparison with their younger counterparts

Ductal carcinoma is the commonest histological type found in invasive breast carcinomas and may be associated with worse prognosis, when compared to non-ductal carcinoma. Older patients tend to display more favourable tumour biology than younger patients. This study aimed to investigate the significance of histological type and its relationship with clinical outcome in the older group. A total of 808 older (≥70 years) women with early operable primary breast cancer underwent surgery as their primary treatment, followed by optimal adjuvant therapies, in the Nottingham Breast Unit between 1973 and 2009. The histological types of the surgical specimens were reviewed and compared with those in a previously characterised younger (<70 years) series (N = 1,733), in terms of distribution and correlation with clinical outcome. Ductal type was associated with a significantly worse clinical outcome when compared to non-ductal type in the older group in terms of 10-year rates of metastasis-free survival (75 vs 79 %, p = 0.028) and overall survival (44 vs 52 %; p = 0.015). Similar worse clinical outcome was found with the ductal type in the younger group in terms of 10-year rates of metastasis-free survival (65 vs 79 %; p = 0.001) and overall survival (60 vs 78 %; p = 0.001). For all patients with ductal type carcinomas, the older series showed significantly better 10-year metastasis-free survival (75 vs 65 %, p < 0.001) and breast cancer-specific survival (75 vs 69 %, p = 0.025) when compared to the younger series. In both old and the young, ductal cancers were associated with poor survival outcome when compared to non-ductal cancers. When compared to their younger counterparts, older patients with ductal type carcinomas had better metastasis-free and breast cancer-specific survival rates (their lower overall survival was likely to be due to death from other causes), despite having a lower likelihood of receiving adjuvant systemic therapy.     

Survival of patients with BRCA1-associated breast cancer diagnosed in an MRI-based surveillance program

We report the 5- and 10-year survival rate of women diagnosed with breast cancer in the context of an annual MRI-based surveillance program. In 2001, as part of a national initiative, women in Norway with a BRCA1 mutation were offered annual screening with breast MRI in addition to mammography. 802 women with a BRCA1 mutation were screened one or more times and followed for a mean of 4.2 years. As of December 2011, 68 of 802 women in the screening program were diagnosed with DCIS or invasive breast cancer (8.5 %), including eight prevalent, 50 incident screen-detected and eight interval cancers. Two latent cancers were detected at prophylactic mastectomy. Sixty-three of the cancers were invasive and five were in situ. The mean tumour size was 1.4 cm (range 0.2–4.5 cm), and 85 % of the patients were node-negative. Ten of the 68 patients died of cancer in the follow-up period. The 5-year breast cancer-specific survival for women with cancer was 75 % (95 % CI 56–86 %) and the 10-year survival was 69 % (95 % CI: 48–83 %). The 5-year survival for women with Stage 1 breast cancer was 82 % compared to 98 % in the population. The 5- and 10-year survival of women with a BRCA1-associated breast cancer detected in a national MRI-based screening program in BRCA1 mutation carriers Norway was less than anticipated. The benefit of annual MRI surveillance on reducing breast cancer mortality in BRCA1 mutation carriers remains to be proven.     

The prognostic effect of estrogen receptor status differs for younger versus older breast cancer patients

Purpose

To estimate the prognostic impact of estrogen receptor (ER)-status among women with primary invasive breast cancer, according to age at diagnosis.

Methods

We studied 1910 women with primary invasive breast cancer (stages I–III) who were treated at Women’s College Hospital between 1987 and 2000. For each patient, we obtained information on age at diagnosis, tumour size, lymph node status, ER-status, treatments received (radiotherapy, chemotherapy and tamoxifen) and dates and causes of death. Patients were followed from the date of diagnosis until the date of death from breast cancer or the date of last follow-up. We used the Kaplan–Meier method to estimate the 15-year actuarial rates of breast cancer-specific survival for women with ER-positive and ER-negative breast cancer, according to age at diagnosis (categories). We used the Cox proportional hazards model to estimate the adjusted hazard ratios for death from breast cancer associated with positive ER-status (compared to negative ER-status), stratified by age at diagnosis.

Results

We identified 1347 women with ER-positive breast cancer (70.5%) and 563 women with ER-negative breast cancer (29.5%). Among all 1910 women in the cohort, the actuarial rate of breast cancer-specific survival at 15 years was 77% for those with ER-positive breast cancer compared to 70% for those with ER-negative breast cancer (adjusted HR = 0.69; 95% CI 0.56–0.85; p = 0.0006). The prognostic impact of ER-status differed according to age at diagnosis. Among 213 women diagnosed before age 40, breast cancer-specific survival at 15 years was worse for those with ER-positive breast cancer than for those with ER-negative breast cancer (55 vs. 61%; adjusted HR = 0.90; 95% CI 0.57–1.41; p = 0.64). In contrast, among 1697 women diagnosed between ages 40 and 75, breast cancer-specific survival at 15 years was better for those with ER-positive breast cancer than for those with ER-negative breast cancer (78 vs. 72%; adjusted HR = 0.60; 95% CI 0.47–0.76; p < 0.0001).

Conclusions

Positive ER-status is a favourable prognostic factor among women diagnosed with breast cancer at or above age 40, but not among women diagnosed before age 40.

     

Incidence of contralateral breast cancer in Japanese patients with unilateral minimum-risk primary breast cancer,and the benefits of endocrine therapy and radiotherapy

Background:

Tamoxifen is recommended as adjuvant endocrine therapy for patients with minimum-risk breast cancer. It is primarily effective at prevention of contralateral and ipsilateral breast cancer recurrence after breast-conserving surgery. The incidence of contralateral breast cancer and the absolute benefit of endocrine therapy among patients with unilateral minimum-risk breast cancer in Japan, where the incidence of breast cancer is low, are unknown.

Patients and methods

We retrospectively studied the incidence of contralateral breast cancer, and the efficacy of endocrine therapy, in a cohort of 2074 Japanese women with unilateral breast cancer whose primary tumor was pTis (n = 1905) or pT1mic (n = 169) (unknown for endocrine therapy, n = 4; unknown for radiotherapy, n = 2). We also assessed the efficacy of endocrine therapy and radiotherapy for prevention of ipsilateral and contralateral breast cancer recurrence in 1205 patients who underwent breast-conserving surgery (unknown for endocrine therapy, n = 2; unknown for radiotherapy, n = 2).

Results

The incidence of contralateral breast cancer per 1000 person-years was 5.1 (95 % confidence interval (CI), 3.7–7.1) among patients without endocrine therapy (n = 1364) and 3.6 (95 % CI 2.1–6.1) among those with endocrine therapy (n = 706). The incidence of ipsilateral breast cancer recurrence after breast-conserving surgery per 1000 person-years was 9.2 (95 % CI 6.5–13) among patients without endocrine therapy (n = 753) and 4.2 (95 % CI 2.2–8.1) among those with endocrine therapy (n = 450). The incidence of ipsilateral breast cancer recurrence after breast-conserving surgery per 1000 person-years was 9.9 (95 % CI 6.3–15.6) among patients without radiotherapy (n = 380) and 5.9 (95 % CI 3.9–9.0) among those with radiotherapy (n = 823).

Conclusion

The incidence of contralateral breast cancer among minimum-risk breast cancer patients in Japan, where the incidence of breast cancer is low, was similar to that in Western countries. Endocrine therapy is indicated for this population.     

Demographic and clinico-pathological characteristics of breast cancer patients with history of oral alendronate use

Bisphosphonates are the most commonly used agents in the treatment of osteoporosis, and bisphosphonate therapy reduces the risk of skeletally related complications in patients with bone metastases due to malignancy. However, the effect of oral alendronate treatment on clinical and pathological properties of breast cancer has not been reported. Thus, we aimed to investigate retrospectively the demographic and clinico-pathological characteristics of new diagnosis of breast cancer patients with oral alendronate users for longer than 1 year, compared with non-users. Newly diagnosed breast cancer patients from 1998 to 2010 in our clinic were retrospectively analyzed. Patient’s demographics, including survival data and tumor characteristics, were obtained from medical charts. Breast cancer patients who were taking oral alendronate more than 12 months at the time of breast cancer diagnosis were enrolled as an alendronate users (n = 44), where the patients matched with the same age who were not taking oral alendronate were included as a control group (n = 444). A total of 488 patients were included in this study. Forty-four patients received an oral alendronate treatment more than 1 year, and 444 patients were considered as non-users. Median age of both alendronate users and non-users was 57 (33–89). Lower incidence of histological grade III, T3–T4 tumor, and node positivity was seen in alendronate users but not statistically significant. A similar trend for lower incidence of triple negative and higher incidence ER (P = 0.13), progesterone receptor (P = 0.12), and HER2 positivity (P = 0.21) was also seen in alendronate users but not statistically significant. Estimated median disease-free survival was 150 months in alendronate users where as 70 months in non-users (P = 0.015). Five-year survival rate in alendronate users was 97.4 %, whereas in non-users was 89.8 % (P = 0.13). The use of oral alendronate for longer than 1 year at the time of breast cancer diagnosis was associated with better clinico-pathological properties and significantly improved disease-free survival in breast cancer patients.     

The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF-β-signaling pathway: The Breast Cancer Health Disparities Study

The TGF-β signaling pathway regulates cellular proliferation and differentiation. We evaluated genetic variation in this pathway, its association with breast cancer survival, and survival differences by genetic ancestry and self-reported ethnicity. The Breast Cancer Health Disparities Study includes participants from the 4-Corners Breast Cancer Study (n = 1,391 cases) and the San Francisco Bay Area Breast Cancer Study (n = 946 cases) who have been followed for survival. We evaluated 28 genes in the TGF-β signaling pathway using a tagSNP approach. Adaptive rank truncated product (ARTP) was used to test the gene and pathway significance by Native American (NA) ancestry and by self-reported ethnicity (non-Hispanic white (NHW) and Hispanic/NA). Genetic variation in the TGF-β signaling pathway was associated with overall breast cancer survival (P _ARTP = 0.05), especially for women with low NA ancestry (P _ARTP = 0.007) and NHW women (P _ARTP = 0.006). BMP2, BMP4, RUNX1, and TGFBR3 were significantly associated with breast cancer survival overall (P _ARTP = 0.04, 0.02, 0.002, and 0.04, respectively). Among women with low NA, ancestry associations were as follows: BMP4 (P _ARTP = 0.007), BMP6 (P _ARTP = 0.001), GDF10 (P _ARTP = 0.05), RUNX1 (P _ARTP = 0.002), SMAD1 (P _ARTP = 0.05), and TGFBR2 (P _ARTP = 0.02). A polygenic risk model showed that women with low NA ancestry and high numbers of at-risk alleles had twice the risk of dying from breast cancer as did women with high NA ancestry. Our data suggest that genetic variation in the TGF-β signaling pathway influences breast cancer survival. Associations were similar when the analyses were stratified by genetic ancestry or by self-reported ethnicity.     

Association between allergies, asthma, and breast cancer risk among women in Ontario, Canada

Purpose

To investigate the association between allergies, asthma, and breast cancer risk in a large, population-based case–control study.

Methods

Breast cancer cases (n = 3,101) were identified using the Ontario Cancer Registry and population controls (n = 3,471) through random digit dialing. Self-reported histories of allergies, hay fever, and asthma were collected by questionnaire. Logistic regression was used to assess associations between breast cancer risk and history of allergy/hay fever and asthma, with 16 possible confounders examined. Analyses were stratified by menopausal status.

Results

A history of allergies or hay fever was associated with a small reduction in breast cancer risk [age-adjusted odds ratio (AOR) = 0.86, 95 % confidence interval (CI) 0.77–0.96] and did not differ by menopausal status. Asthma was not associated with breast cancer risk overall; however, among premenopausal women, asthma was associated with a reduced risk of breast cancer (AOR = 0.72, 95 % CI 0.54–0.97).

Conclusions

A history of allergies may be associated with a modest reduction in breast cancer risk. Asthma does not appear to be associated with breast cancer risk overall; however, asthma may be associated with reduced breast cancer risk among premenopausal women.     

Radioguided Occult Lesion Localisation Versus Wire-Guided Lumpectomy in the Treatment of Non-Palpable Breast Lesions

The purpose of this study was to compare the two methods—guidewire localisation and the radioguided occult lesion localisation—used in the localisation and surgical removal of non-palpable breast tumours. This retrospective study enrolled patients diagnosed with nonpalpable malignant breast tumours. In this study either guidewire localisation (GWL, n?=?69) or radioguided occult lesion localisation (ROLL, n?=?321) was used for the detection and removal of the tumours. The two methods were compared with regards to preoperative localisation time, operating time, removed specimen volume, the pathological tumour size, the presence of positive surgical margins and postoperative complications. Furthermore, we have also investigated other factors that could have an impact on the frequency of positive resection margins. The localisation time was significantly shorter in the ROLL group, both with ultrasound guidance (5.7?±?1.44 min vs. 21.6?±?2.37 min, p?=?0.05) and with radiographic guidance (21.8?±?3.1 min vs. 41.6?±?3.75 min, p?=?0.021) as well. No significant difference was observed between the two methods in terms of operating time, removed specimen volume and pathological tumour size, or the presence of positive resection margins, or the occurrence of postoperative wound infections. The size of the tumour (ROLL, GWL grps), the presence of a multifocal tumour (ROLL grp), the presence of an extensive in situ breast carcinoma around the invasive cancer (ROLL, GWL grps) and the volume of the removed breast specimen (GWL grp) significantly increased the frequency of positive resection margins. We recommend the use of the ROLL method for the removal of nonpalpable breast tumours as it has a much shorter localisation time, and it is a simpler surgical technique as well.     

Grand multiparity and reproductive cancer in the Jerusalem Perinatal Study Cohort

Objectives

Grand multiparity is associated with reduced mortality from reproductive cancers. We aimed to separate the components of mortality, by measuring incidence of and survival after reproductive cancer onset in grand multiparous compared to other parous women.

Study design

We linked data from the population-based Jerusalem Perinatal Study Cohort, which included women aged 13–55 who delivered 1964–1976, with Israel’s National Cancer Registry. We compared breast and gynecologic cancer risk and all-cause survival following a cancer diagnosis, among grand multiparae (GMPs = parity 5+, n = 8,246) versus women with parity 1–4 (n = 19,703), adjusting for reproductive and demographic variables.

Results

Grand multiparae were at significantly lower risk of breast cancer than others (adjusted hazard ratio (HR_adj) = 0.62, 95 % confidence interval (CI) 0.54–0.71), after controlling for age at first birth, education, and other covariates. This reduction was greater among GMPs whose first birth occurred after age 30 (p-interaction = 0.0001) and for cancer occurring before age 50 years (p = 0.002). In contrast, GMPs were at greater risk of death than women with parity <5, following a breast cancer diagnosis (HR_adj = 1.69, CI 1.39–2.1). Ovarian, uterine, and cervical cancer incidence did not differ between the groups, but survival was reduced for GMPs with uterine cancer (HR_adj = 2.48, CI 1.22–5.03).

Conclusion

Reduced reproductive cancer mortality reported among GMPs masks two opposing phenomena: decreased breast cancer risk and poorer survival after breast and uterine cancers. The latter unfavorable outcome suggests that tumors in GMPs may be particularly aggressive, having perhaps escaped protective mechanisms conferred by parity. This finding calls for heightened clinical attention in this group.

     

MAGEC2, an epithelial-mesenchymal transition inducer,is associated with breast cancer metastasis

MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.     

Influence of hospital surgical volume of radical prostatectomy on quality of perioperative care

Purpose

We investigated the relationships between hospital surgical volume, surgical outcome, care plans indicated in critical pathways and actual perioperative care using data from a nationwide survey for radical prostatectomy.

Materials and methods

In this study, urologists from 155 hospitals in Japan cooperated in submitting the data of 4,029 patients who underwent radical prostatectomy in 2007, and the perioperative care plan in critical pathways. Of these, we analyzed data of 3,499 patients undergoing open radical prostatectomy and minimum incision endoscopic radical prostatectomy.

Results

Increasing hospital volume was associated with decreased proportion of open radical prostatectomy (p < 0.001). As the hospital volume increased, surgical duration was significantly shorter (p < 0.001) and bleeding volume decreased (p < 0.004). Analyses of perioperative care suggested that low-volume hospitals (<15 patients annually) were likely to have longer care than medium-volume (15–29 patients per year) or high-volume (≥30 patients per year) hospitals, and the length of actual care was prolonged in the low-volume hospitals. Multivariate logistic regression analysis suggested that the occurrence of postoperative complications was significantly associated with surgeon’s volume (p = 0.004), patient age (p = 0.001), preoperative anticoagulant therapy (p = 0.045), coexistent diabetes mellitus (p = 0.009), surgical duration (p = 0.002) and bleeding volume (p < 0.001), but not hospital volume.

Conclusions

Urologists in high-volume hospitals appeared to attempt new types of surgery. Hospital surgical volume was strongly associated with the surgical duration, bleeding volume and planned and actual perioperative care; however, it was not associated with postoperative complications.     

Contralateral mastectomy improves survival in women with BRCA1/2-associated breast cancer

BRCA1/2 mutation carriers with breast cancer are at high risk of contralateral disease. Such women often elect to have contralateral risk-reducing mastectomy (CRRM) to reduce the likelihood of recurrence. This study considers whether CRRM improves overall survival. 105 female BRCA1/2 mutation carriers with unilateral breast cancer who underwent CRRM were compared to controls (593 mutation carriers and 105 specifically matched) not undergoing CRRM and diagnosed between 1985 and 2010. Survival was assessed by proportional hazards models, and extended to a matched analysis using stratification by risk-reducing bilateral salpingo-oophorectomy (RRBSO), gene, grade and stage. Median time to CRRM was 1.1 years after the primary diagnosis (range 0.0–13.3). Median follow-up was 9.7 years in the CRRM group and 8.6 in the non-CRRM group. The 10-year overall survival was 89 % in women electing for CRRM (n = 105) compared to 71 % in the non-CRRM group (n = 593); p < 0.001. The survival advantage remained after matching for oophorectomy, gene, grade and stage: HR 0.37 (0.17–0.80, p = 0.008)—CRRM appeared to act independently of RRBSO. CRRM appears to confer a survival advantage. If this finding is confirmed in a larger series it should form part of the counselling procedure at diagnosis of the primary tumour. The indication for CRRM in women who have had RRBSO also requires further research.     

Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ

Background

The natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear.

Disparities in survival after female breast cancer diagnosis: a population-based study

Background

Despite advances in treatment and increased screening, female breast cancer survival is affected by race, ethnicity, and socioeconomic status (SES). The purpose of this study was to substantiate disparities in breast cancer mortality in a large and unique dataset containing 7 distinct racial groups, 31 comorbidities, demographic and clinical/pathological patient characteristics, and neighborhood poverty information.

Methods

Florida Cancer Data System registry (1996–2007) linked with the Agency for Health Care Administration and U.S. Census tract (n = 127,754) explored median survival and 1-, 3-, and 5-year survival rates by the Kaplan–Meier method. Log-rank tests compared survival curves by race/ethnicity/SES. Cox proportional hazards regression models were used to obtain unadjusted and adjusted hazard ratios (HR) and 95 % confidence intervals.

Results

Native Americans had the lowest median survival (7.4 years) and Asians had the highest (12.6 years). For the univariate analysis, worse survival was seen for blacks (HR = 1.44; p < 0.001) and better survival for Asians (HR = 0.71; p < 0.001), Asian Indians or Pakistanis (HR = 0.65; p = 0.013), and Hispanics (HR = 0.92; p < 0.001). Multivariate analysis demonstrated sustained survival detriment for blacks (HR = 1.28; p < 0.001) and improved survival for Hispanics (HR = 0.90; p = 0.001). For SES, there was an incremental improvement in survival for each higher SES category in all analyses (p < 0.001).

Conclusions

Utilizing a large enriched state cancer registry controlling for multiple demographic, clinical, and comorbidities, we fully explored survival disparities in female breast cancer and found certain aspects of race, ethnicity, and SES to remain significantly associated with breast cancer survival. More research is needed to uncover the source of these ongoing disparities.     

Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma

CUB and SUSHI multiple domain protein 1 (CSMD1) is a candidate tumour suppressor gene that maps to chromosome 8p23, a region deleted in many tumour types including 50% of breast cancers. CSMD1 has homologies to proteins implicated in carcinogenesis. We aimed to study the expression pattern of the CSMD1 protein and evaluate its prognostic importance in invasive ductal carcinoma (IDC). An anti-CSMD1 antibody was developed and validated. The expression pattern of CSMD1 in normal breast and IDC samples was investigated by immunohistochemistry in 275 patients. Univariate and multivariate Cox regression analyses were performed. In normal breast duct epithelial cells, luminal, membranous and cytoplasmic CSMD1 staining was identified. Reduced expression of CSMD1 was detected in 79/275 (28.7%) of IDC cases. Low CSMD1 expression was significantly associated with high tumour grade (P = 0.003). CSMD1 expression was associated with overall survival (OS; HR = 0.607, 95%CI: 0.4–0.91, P = 0.018) but not with disease-free survival (DFS; HR = 0.81, 95%CI: 0.46–1.43, P = 0.48). Multivariate analysis showed that CSMD1, together with Nottingham Prognostic Index, was considered an independent predictor of OS (HR = 0.607, 95%CI: 0.4–0.91, P = 0.018) but not DFS (HR = 0.84, 95%CI: 0.46–1.5, P = 0.573). Reduction of CSMD1 expression was significantly associated with high tumour grade and decreased OS. Therefore, our results support the idea that CSMD1 is a tumour suppressor gene and suggest its possible use as a new prognostic biomarker. The membrane expression pattern of CSMD1 suggests that it may be a receptor or co-receptor involved in the process of signal transduction.     

Contralateral prophylactic mastectomy and survival: report from the National Cancer Data Base, 1998–2002

The use of contralateral prophylactic mastectomy (CPM) has been increasing despite questionable survival benefit. We examined the effect of CPM on survival using the National Cancer Data Base. We examined overall survival on 219,983 mastectomy patients diagnosed with unilateral AJCC Stage 1–III invasive breast cancer between 1998 and 2002 of which 14,994 (7 %) underwent CPM at the time of their index mastectomy. Median follow up time was 5 years. Neoadjuvant and locally advanced breast cancers were excluded. Approximately 4 % underwent CPM in 1998 compared to 9.4 % in 2002, an ~125 % increase. CPM patients were significantly younger than non-CPM patients, on managed care plans, and were treated at high volume centers. The unadjusted hazard ratio (HR) of death was 0.55 (95 % CI 0.52–0.57) for CPM compared to unilateral mastectomy. In a multivariable Cox model adjusting for age, race, stage, grade, histology, insurance, facility characteristics, use of adjuvant hormonal, chemotherapy, and radiotherapy, and year of diagnosis, the adjusted HR was 0.88 (95 % CI 0.83–0.93; p < 0.001) which translated into an absolute 5-year benefit of 2 %. There was a differential effect of CPM by stage and age: HR = 0.88 (95 % CI 0.82–0.94; p < 0.001) in women younger than 70 with stage I/II, and HR = 0.95 (95 % CI 0.88–1.04; p = 0.28) in women with stage III or older than age 69 which translated into an absolute 5-year benefit of 1.3 %. Utilization of hormonal therapy or chemotherapy had no effect on the HR. After adjusting for confounding, the overall survival benefit for CPM is minimal at best.     

A population-based audit of surgical practice and outcomes of oncoplastic breast conservations in Scotland – An analysis of 589 patients

Introduction

Current evidence for oncoplastic breast conservation (OBC) is based on single institutional series. Therefore, we carried out a population-based audit of OBC practice and outcomes in Scotland.