Prognosis of metachronous contralateral breast cancer: importance of stage, age and interval time between the two diagnoses

Studies comparing the prognosis after contralateral breast cancer (CBC) with that after unilateral breast cancer (UBC) shows conflicting results. We assessed the risk of breast cancer-specific death for women with metachronous CBC compared to those with a UBC in 8,478 women with invasive primary breast cancer registered in the Guy’s and St. Thomas’ Breast Cancer Tissue and Data Bank. Risk factors associated with breast cancer-specific death for women with CBC were estimated using Cox proportional hazards modelling. Prognoses after UBC and CBC were compared, with survival time for women with CBC calculated: (i) from CBC, (ii) from the initial cancer with CBC as a time-dependent covariate. Women diagnosed with CBC within 5 years after the initial primary breast cancer had a worse prognosis than those with CBC after 5 years and those with UBC. Women with CBC who had positive lymph nodes at the initial breast cancer diagnosis were at an increased risk of dying from breast cancer compared to those without [HR 2.5 (95% CI 1.5–4.0)]. For all stages of the initial breast cancer, a worse prognosis was observed after CBC. CBC increased the hazard originating from the initial cancer at any follow-up time, but the highest hazards were associated with a short interval to CBC. Metachronous CBC adds to the risk of dying from breast cancer. The risk increases substantially when it occurs shortly after the initial cancer, indicating a CBC in some instances may be an indicator of active distant disease. The occurrence of CBC implies a new surveillance and therapeutic situation.     

Hormone receptor status of contralateral breast cancers: analysis of data from the US SEER population-based registries

Background

Women diagnosed with breast cancer display higher propensity to develop second primary cancer in the contralateral breast (CBC). Identification of patients with increased risk of CBC and understanding relationships between hormone receptor (HR) statuses of the first and second breast cancers is desirable for endocrine-based prevention strategies.

Methods

Using 1992–2012 data from 13 SEER registries, the risk of developing CBC was determined as ratio of observed and expected second breast cancers (SIR). Association between HR statuses was examined by exploratory data analysis and multivariable logistic regression. Results: Women with ER-positive and ER-negative breast cancers have increased risk of developing CBC with SIR values 2.09 (CI 95 = 1.97–2.21) and 2.40 (CI 95 = 2.18–2.63), respectively. ER statuses of the CBC are moderately positively associated. In metachronous CBC, most cases with ER-positive first cancers had ER-positive second breast cancers (81.6 %; CI 95 = 80.2–82.9 %); however, considerable proportion of cases with ER-negative first cancers had ER-positive second cancers (48.8 %; CI 95 = 46.2–51.4 %).

Conclusions

Some women with ER-negative breast cancers may benefit from endocrine-based prevention of ER-positive CBC.

     

Patterns of metastasis in women with metachronous contralateral breast cancer

Background:

The understanding of metastatic patterns after metachronous contralateral breast cancer (CBC) may help determine the biological nature of CBC.

Methods:

A cohort of 8478 women with breast cancer treated at Guy''s and St Thomas'' NHS Foundation Trust between 1975 and 2006 were studied. Organ-specific 5-year cumulative incidence and incidence rate ratios were assessed for women diagnosed with unilateral breast cancer (UBC), CBC within 5 years and CBC more than 5 years of the initial diagnosis.

Results:

Women diagnosed with CBC within 5 years had a higher incidence of metastases in all organs compared with UBC. Women with a short interval time to CBC developed metastasis more rapidly and were more likely to develop visceral and distant cutaneous metastases compared with bone metastasis.

Conclusion:

These findings explain poor prognosis of women with early occurring CBC and suggest that some of these CBCs are indicators of aggressive and/or systemic disease.     

Mammography interval and breast cancer mortality in women over the age of 75

The purpose of this study is to evaluate the relationship between mammography interval and breast cancer mortality among older women with breast cancer. The study population included 1,914 women diagnosed with invasive breast cancer at age 75 or later during their participation in the Women’s health initiative, with an average follow-up of 4.4 years (3.1 SD). Cause of death was based on medical record review. Mammography interval was defined as the time between the last self-reported mammogram 7 or more months prior to diagnosis, and the date of diagnosis. Multivariable adjusted hazard ratios (HR) and 95 % confidence intervals (CIs) for breast cancer mortality and all-cause mortality were computed from Cox proportional hazards analyses. Prior mammograms were reported by 73.0 % of women from 7 months to ≤2 year of diagnosis (referent group), 19.4 % (>2 to <5 years), and 7.5 % (≥5 years or no prior mammogram). Women with the longest versus shortest intervals had more poorly differentiated (28.5 % vs. 22.7 %), advanced stage (25.7 % vs. 22.9 %), and estrogen receptor negative tumors (20.9 % vs. 13.1 %). Compared to the referent group, women with intervals of >2 to <5 years or ≥5 years had an increased risk of breast cancer mortality (HR 1.62, 95 % CI 1.03–2.54) and (HR 2.80, 95 % CI 1.57–5.00), respectively, p trend = 0.0002. There was no significant relationship between mammography interval and other causes of death. These results suggest a continued role for screening mammography among women 75 years of age and older.     

Stage at diagnosis and mortality in women with pregnancy-associated breast cancer (PABC)

Converging evidence indicates that women with pregnancy-associated breast cancer (PABC) have increased mortality compared to women with breast cancer not diagnosed near pregnancy (non-PABC). Our aim was to investigate if the stage distribution differs between PABC and non-PABC and if stage at diagnosis can explain the poorer prognosis observed among women with PABC. We identified 3,282 breast cancers in women aged 15–44 years at diagnosis for whom staging data (tumor size, nodal involvement, metastasis) were available in the Swedish Cancer Register between 2002 and 2009. Information on reproductive history and vital status was obtained from the Multi-Generation Register and the Cause of Death Register. PABC was defined as breast cancers diagnosed during pregnancy and up to 2 years after delivery (n = 317). Non-PABC was defined as cases diagnosed before pregnancy or more than 2 years postpartum. Stage distributions were compared between PABC and non-PABC, and mortality rates were modeled using Cox regression. Compared to women with non-PABC, the mortality was almost 50 % higher in women with PABC [unadjusted hazard ratio (HR) 1.47 (95 % CI 1.04–2.08)], a difference which was reduced after adjustment for age and calendar year of diagnosis [HR 1.27 (95 % CI 0.88–1.83)]. Although advanced stage of breast cancer at diagnosis was more common among PABC than among non-PABC, further adjustment for stage only slightly reduced the HR [1.22 (95 % CI 0.84–1.78)]. The difference in mortality between PABC and non-PABC was more pronounced among women above 35 years and among women with PABC diagnosed within 1 year postpartum. Age, rather than stage at diagnosis, appears to act as the principal driver of the increased mortality observed in women with PABC. However, these findings do not preclude an untoward influence on mortality by pregnancy-associated factors affecting tumor aggressiveness and progression.     

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.     

Alcohol consumption and cigarette smoking in combination: A predictor of contralateral breast cancer risk in the WECARE study

Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a large population‐based case‐control study of women with breast cancer where cases (N = 1,521) had asynchronous CBC and controls (N = 2,212), matched on survival time and other factors, had unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease characteristics and other factors. There was some evidence for an association between CBC risk and current drinking or current smoking at the time of first breast cancer diagnosis, but the increased risk occurred primarily among women exposed to both (RR = 1.62, 95% CI 1.24–2.11). CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR = 1.54, 95% CI 1.18–1.99). In the subset of women with detailed information on amount consumed, smoking an average of ≥10 cigarettes per day following diagnosis was also associated with increased CBC risk (RR = 1.50, 95% CI 1.08–2.08; p‐trend = 0.03). Among women with a diagnosis of breast cancer, information on current drinking and smoking could contribute to the prediction of CBC risk. Women who both drink and smoke may represent a group who merit targeted lifestyle intervention to modify their risk of CBC.     

Comorbidities and breast cancer survival: a report from the Shanghai Breast Cancer Survival Study

We investigated the association of major comorbidities with breast cancer outcomes using the Shanghai Breast Cancer Survival Study, a population-based, prospective cohort study of Chinese women diagnosed with breast cancer. Analyses included 4,664 women diagnosed with stage I–III incident breast cancer aged 20–75 years (median age = 51) during 2002–2006. Women were interviewed at 3–11 months post-diagnosis (median = 6.4) and followed up by in-person interviews and linkage with the vital statistics registry. Multivariable hazard ratios (HRs) and (95 % confidence intervals (CIs)) for the associations of comorbidities with breast cancer outcomes were estimated using Cox regression models. After a median follow-up of 5.3 years (range: 0.64–8.9), 647 women died (516 from breast cancer) and 632 recurrence/metastases were documented. The main comorbidities reported included: hypertension (22.4 %), chronic gastritis (14.3 %), diabetes mellitus (6.2 %), chronic bronchitis/asthma (5.8 %), coronary heart disease (5.0 %), and stroke (2.2 %). Diabetes was associated with increased risk of total mortality (adjusted HR: 1.40 (1.06–1.85)) and non-breast cancer mortality (adjusted HR: 2.64 (1.63–4.27)), but not breast cancer-specific mortality (adjusted HR: 0.98 (0.68–1.41)), adjusting for socio-demographics, clinical characteristics, selected lifestyle factors, and other comorbidities. Women with a history of stroke had a non-significant increased risk of total mortality (adjusted HR: 1.42 (0.91–2.22)) and a significant increased risk of non-breast cancer mortality (adjusted HR: 2.52 (1.33–4.78)), but not breast cancer-specific mortality (adjusted HR: 0.78 (0.38–1.62)). Overall, none of the comorbidities investigated were significantly associated with recurrence. In this large prospective cohort of breast cancer survivors, diabetes was significantly associated with increased risk of total and non-breast cancer mortality, and history of stroke was associated with increased risk of non-breast cancer mortality.     

Long-term prognosis of early-onset breast cancer in a population-based cohort with a known BRCA1/2 mutation status

All women in the South Sweden Health Care Region with breast cancer diagnosed aged less than 41 during the period between 1990 and 1995 were contacted in 1996 and offered germline mutation analysis of the BRCA1 and BRCA2 genes. Mutation carriers (n = 20) were compared with noncarriers (n = 201) for overall survival (OS) and risk of contralateral breast cancer (CBC). Mutation carriers were younger at diagnosis and more likely to have ER-negative, PgR-negative and grade III tumors. Median follow-up was 19 years. The 5-, 10-, 15-, and 20-year OS were 60, 45, 39, and 39 % for mutation carriers and 82, 70, 59, and 53 % for noncarriers, respectively (5-year log-rank P = 0.013; 10-year P = 0.008; 15-year P = 0.020; and 20-year P = 0.046). In univariable analysis, there was a trend for an inferior OS for mutation carriers (HR 1.8; 95 % CI 1.0–3.3). When stratified for use of (neo)adjuvant chemotherapy, an inferior OS was significant only for the subgroup of patients who did not receive chemotherapy (HR 3.0; 95 % CI 1.2–7.7). In multivarible analysis, BRCA1/2 mutation status was a significant predictor of OS when adjusting for tumor stage, age, and use of chemotherapy, but not when ER status was also included in the model. The 15-year cumulative risk of CBC was 53 % for mutation carriers and 10 % for noncarriers (HR 5.9; 95 % CI 1.9–18.6); among the noncarriers the risks were 5, 22, and 30 % for patients without close relatives having breast cancer, with second-degree relatives having breast cancer, and with firstdegree relatives with breast cancer, respectively. In conclusion, the poor prognosis of young BRCA1/2 mutation carriers with breast cancer is mainly explained by the prevalent occurrence of negative prognostic factors rather than mutation status per se, and can to at least some extent be abrogated by the use of chemotherapy.     

Breast cancer in postmenopausal women after non-melanomatous skin cancer: the Women’s Health Initiative observational study

An increased risk of breast cancer has been reported in patients with non-melanomatous skin cancer (NMSC), but this association has not been studied in a large, multi-geographic population. We utilized data from the Women’s Health Initiative observational study to assess whether history of NMSC is associated with breast cancer risk. This analysis included 70,246 postmenopausal White and Hispanic women aged 50–79, in which 4,247 breast cancer cases were identified over a mean (SD) of 11.3 (3.2) years. Baseline information was collected on demographics, medical history, sun exposure, and vitamin D intake. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs). The relationship between NMSC and breast cancer was examined as a time-dependent exposure using updated information on NMSC gathered during follow-up visits. All statistical tests were two sided. There were 5,595 women diagnosed with NMSC at study entry. The annualized rate of breast cancer was 0.64 % among women with a history of NMSC and 0.55 % among women with no history of NMSC. The multivariable-adjusted HR for breast cancer among women with a history of NMSC versus no history of NMSC was 1.07 (95 % CI 0.95–1.20, P = 0.27). Further evaluation stratified by tumor characteristics showed an increased risk of lymph node-positive disease, HR = 1.30 (95 % CI 1.01–1.67, P = 0.04), and regional-stage disease, HR = 1.33 (95 % CI 1.05–1.70, P = 0.02), among women with NMSC. There was no significant overall association between NMSC and breast cancer; however, there was an increased risk of more advanced-stage breast cancer which needs further exploration.     

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study

The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985--1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2*1100delC variant carriers (rate ratio (RR)=1.8, 95% confidence interval (CI)=0.6-5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI=0.8-8.7). We found no significant associations between the CHEK2*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population.     

Long-term risk of medical conditions associated with breast cancer treatment

Early and late effects of cancer treatment are of increasing concern with growing survivor populations, but relevant data are sparse. We sought to determine the prevalence and hazard ratio of such effects in breast cancer cases. Women with invasive breast cancer and women with no cancer history recruited for a cancer research cohort completed a mailed questionnaire at a median of 10 years post-diagnosis or matched reference year (for the women without cancer). Reported medical conditions including lymphedema, osteopenia, osteoporosis, and heart disease (congestive heart failure, myocardial infarction, coronary heart disease) were assessed in relation to breast cancer therapy and time since diagnosis using Cox regression. The proportion of women currently receiving treatment for these conditions was calculated. Study participants included 2,535 women with breast cancer and 2,428 women without cancer (response rates 66.0 % and 50.4 %, respectively) Women with breast cancer had an increased risk of lymphedema (Hazard ratio (HR) 8.6; 95 % confidence interval (CI) 6.3–11.6), osteopenia (HR 2.1; 95 % CI 1.8–2.4), and osteoporosis (HR 1.5; 95 % CI 1.2–1.9) but not heart disease, compared to women without cancer Hazard ratios varied by treatment and time since diagnosis. Overall, 49.3 % of breast cancer cases reported at least one medical condition, and at 10 or more years post-diagnosis, 37.7 % were currently receiving condition-related treatment. Responses from survivors a decade following cancer diagnosis demonstrate substantial treatment-related morbidity, and emphasize the need for continued medical surveillance and follow-up care into the second decade post-diagnosis.     

Adolescent physical activity in relation to breast cancer risk

Adolescent physical activity may protect against premenopausal breast cancer. Whether it also prevents postmenopausal breast cancer, and whether associations are independent of adult activity, is unclear. We evaluated this association among 75,669 women in the Nurses’ Health Study II. In 1997, participants reported strenuous, moderate, and walking activity (hours/week) at ages 12–13, 14–17, 18–22, and 23–29 years. We estimated metabolic equivalent task hours (MET-h)/week. Participants also reported current physical activity over follow-up. Breast cancer diagnoses (n = 2,697; premenopausal = 1,351; postmenopausal = 965) through 2011 were reported by participants and confirmed with medical records. We additionally stratified analyses by median age at diagnosis. In Cox proportional hazards models adjusted for adolescent characteristics, physical activity from ages 14–22 was modestly inversely associated with premenopausal breast cancer [e.g., hazard ratio (HR) comparing 72+ to <21 MET-h/week 0.81 (95 % confidence interval (CI) 0.69–0.95; p-trend = 0.10) for ages 14–17 and 0.85 (95 % CI 0.71–1.02; p-trend = 0.06 for ages 18–22]. However, adjustment for adult activity and additional breast cancer risk factors attenuated the associations [ages 14–17: 0.85 (95 % CI 0.73–1.00; p-trend = 0.33)]. Associations were stronger among women diagnosed at younger ages [e.g., ages 18–22, HR 0.77 (95 % CI 0.60–0.99; p-trend = 0.05) for women diagnosed before 46.9 years; HR 1.02 (95 % CI 0.79–1.32; p-trend = 0.94) for those diagnosed at/after 46.9 years]. Early life physical activity was not associated with postmenopausal breast cancer. Overall, adolescent physical activity was not associated with breast cancer risk. However, we observed a suggestive inverse association of physical activity at ages 14–22 years with premenopausal breast cancer.     

Survival from contralateral breast cancer

First primary, or unilateral, breast cancer (UBC) cases diagnosed in 1960–89 at the Cancer Institute (WIA), Chennai, India were followedup until December 31, 1994. Patients with UBC (n=3163) and those who developed second cancer in the contralateral breast (CBC) after the initial breast cancer (n=67 or 2.1% of UBC) were analysed.Compared to UBC patients, those who developed CBC were younger at the time of diagnosis of initial breast cancer and had higher frequency of breast cancer among the family members. The relative survival rate takes into account competing causes of death and was estimated as the ratio of observed survival rate to the expected survival rate. The cumulative relative survival from UBC at 5 and 10 years were 51% and 41%, respectively, and the corresponding rates for CBC were 47 and 30% the survival difference seen between UBC and CBC patients was not statistically significant. The survival rates among younger, middle-aged and older women were significantly different from each other in UBC but not in CBC patients. Both UBC and CBC with early stage disease had a better survival compared to late stage disease. Survival advantage was also seen among both UBC and CBC patients with family history of breast cancer compared to those without. The multivariate analysis by the life table proportional hazards model showed that the age at diagnosis is an independent prognostic factor for breast cancer. The study results should be interpreted in the light of small sample size of second cancers.     

Post-diagnosis physical activity and survival after breast cancer diagnosis: the Long Island Breast Cancer Study

Physical activity (PA) is associated with physiological responses thought to beneficially affect survival after breast cancer diagnosis, yet few studies have considered the entire survivorship experience. Effects of post-diagnosis activity on survival were examined in a cohort of 1,423 women diagnosed with in situ or invasive breast cancer in 1996–1997. Subjects were interviewed soon after diagnosis and again after approximately 5 years to assess breast cancer-related factors, including recreational PA before and after diagnosis. Date and cause of death through 2009 were determined from the National Death Index. Adjusted estimates were obtained using proportional hazards regression and a selection model to account for missing data. Survival was improved among women who were highly active after diagnosis (>9.0 MET h/week) compared to inactive women (0 MET h/week) for all-cause [hazard ratio (HR) (95 % credible interval): 0.33 (0.22, 0.48)] and breast cancer-specific mortality [HR: 0.27 (0.15, 0.46)]. The association of PA with overall mortality appeared stronger in the first 2 years after diagnosis [HR: 0.14 (0.03, 0.44)] compared to 2+ years since diagnosis [HR: 0.37 (0.25, 0.55)]. These findings show that post-diagnosis PA is associated with improved survival among women with breast cancer.     

Hypothesized role of pregnancy hormones on HER2+ breast tumor development

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (≤10 or >10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies ≥1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR? = ER? and PR?) expression and HER2 status: HR+/HER2?, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2? tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2? cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of ≤10 years (OR = 1.68; 95 % CI, 1.12–2.52). The effect was present across all source populations and independent of the HR status of the HER2+ tumor. Adjusting for age at diagnosis (≤45 or >45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08–2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.     

Post-surgical highly sensitive C-reactive protein and prognosis in early-stage breast cancer

Obesity, associated with inflammation, has been linked to poor prognosis in breast cancer. Research investigating the potential role of C-reactive protein (CRP), an obesity-associated systemic marker of inflammation, as a mediator of adverse prognostic effects of obesity has yielded inconsistent results. We examined the association of highly sensitive CRP (hsCRP) with obesity-related factors and breast cancer outcome. A cohort of 535 non-diabetic women diagnosed with T1-3, N0-1, M0 breast cancer, was assembled between 1989 and 1996 and followed prospectively. Circulating levels of hsCRP were analyzed on blood obtained postoperatively, prior to systemic therapy, in 501 women. Correlations and prognostic associations were analyzed using one-way analysis of variance, Spearman’s rank correlation coefficients (r) and Cox models. hsCRP was significantly correlated with body mass index (r = 0.60), insulin (r = 0.44), leptin (r = 0.54), and lipids, but not T or N stage, grade or estrogen receptor/progesterone receptor. At a median follow-up of 12 years, hsCRP was not associated with distant disease-free survival or overall survival in univariable [Q4 vs. Q1 hazard ratio (HR) 1.03, 95 % confidence interval (CI) 0.69–1.52, P = 0.9 and HR 1.27, 95 % CI 0.86–1.86, P = 0.24, respectively] or multivariable [Q4 vs Q1 HR 1.02, 95 % CI 0.66–1.59, P = 0.93 and HR 1.17, 95 % CI 0.76–1.81, P = 0.48 respectively] analyses. hsCRP was associated with age, comorbidities, and the insulin resistance syndrome but not with breast cancer outcome.     

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.

     

Duration of tamoxifen use and the risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80 %. Tamoxifen treatment of the first cancer has been associated with a reduction in the risk of a subsequent contralateral cancer. We studied 1,504 women with a known BRCA1 or BRCA2 mutation, 411 women with bilateral breast cancer (cases) and 1,093 women with unilateral breast cancer (controls) in a matched case–control study. Control women were of similar age and had a similar age of diagnosis of first breast cancer as the cases. For each woman who used tamoxifen, the starting and stopping dates were abstracted and the duration of tamoxifen use was calculated. Three hundred and thirty-one women had used tamoxifen (22 %); of these 84 (25 %) had completed four or more years of tamoxifen, the remainder stopped prematurely or were current users. For women with up to 1 year of tamoxifen use, the odds ratio for contralateral breast cancer was 0.37 (95 % CI 0.20–0.69; p = 0.001) compared to women with no tamoxifen use. Among women with 1–4 years of tamoxifen use the odds ratio was 0.53 (95 % CI 0.32–0.87; p = 0.01). Among women with four or more years of tamoxifen use the odds ratio was 0.83 (95 % CI 0.44–1.55; p = 0.55). Short-term use of tamoxifen for chemoprevention in BRCA1 and BRCA2 mutation carriers may be as effective as a conventional 5-year course of treatment.     

Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study

The potential effects of oral contraceptive (OC) and postmenopausal hormone (PMH) use are not well understood among BRCA1 or BRCA2 (BRCA1/2) deleterious mutation carriers with a history of breast cancer. We investigated the association between OC and PMH use and risk of contralateral breast cancer (CBC) in the WECARE (Women’s Environment, Cancer, and Radiation Epidemiology) Study. The WECARE Study is a population-based case-control study of 705 women with asynchronous CBC and 1,398 women with unilateral breast cancer, including 181 BRCA1/2 mutation carriers. Risk-factor information was assessed by telephone interview. Mutation status was measured using denaturing high-performance liquid chromatography followed by direct sequencing in all participants. Outcomes, treatment, and tumor characteristics were abstracted from medical records. Ever use of OCs was not associated with risk among noncarriers (RR = 0.87; 95% CI = 0.66–1.15) or BRCA2 carriers (RR = 0.82; 95% CI = 0.21–3.13). BRCA1 carriers who used OCs had a nonsignificant greater risk than nonusers (RR = 2.38; 95% CI = 0.72–7.83). Total duration of OC use and at least 5 years of use before age 30 were associated with a nonsignificant increased risk among mutation carriers but not among noncarriers. Few women had ever used PMH and we found no significant associations between lifetime use and CBC risk among carriers and noncarriers. In conclusion, the association between OC/PMH use and risk of CBC does not differ significantly between carriers and noncarriers; however, because carriers have a higher baseline risk of second primaries, even a potential small increase in risk as a result of OC use may be clinically relevant.