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.     

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.     

Genome-wide DNA methylation profiling reveals parity-associated hypermethylation of FOXA1

Early pregnancy in women by the age of 20 is known to have a profound effect on reduction of lifelong breast cancer risk as compared to their nulliparous counterparts. Additional pregnancies further enhance the protection against breast cancer development. Nationwide trend of delayed pregnancy may contribute to the recently reported increase in the incidence of advanced breast cancer among young women in this country. The underlying mechanism for the parity-associated reduction of breast cancer risk is not clearly understood. The purpose of the current study is to use whole-genome DNA methylation profiling to explore a potential association between parity and epigenetic changes in breast tissue from women with early parity and nulliparity. Breast tissue was collected from age-matched cancer-free women with early parity (age < 20; n = 15) or nulliparity (n = 13). The methyl-CpG binding domain-based capture-sequencing technology was used for whole-genome DNA methylation profiling. Potential parity-associated hypermethylated genes were further verified by locus-specific pyrosequencing, using an expanded cohort of parous (n = 19) and nulliparous (n = 16) women that included the initial samples used in the global analysis. Our study identified six genes that are hypermethylated in the parous group (P < 0.05). Pyrosequencing confirmed parity-associated hypermethylation at multiple CpG islands of the FOXA1 gene, which encodes a pioneer factor that facilitates chromatin binding of estrogen receptor α. Our work identifies several potential methylation biomarkers for parity-associated breast cancer risk assessment. In addition, the results are consistent with the notion that parity-associated epigenetic silencing of FOXA1 contributes to long-term attenuation of the estrogenic impact on breast cancer development.     

Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time

Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings demonstrate the dynamic nature of the human MD xenograft model, providing a platform for studying the biomolecular basis of MD-associated cancer risk.     

Current or recent pregnancy is associated with adverse pathologic features but not impaired survival in early breast cancer

BACKGROUND:

Pregnancy‐associated breast cancer (PABC) may be defined as breast cancer diagnosed during pregnancy or within 1 year of giving birth. Conflicting data exist regarding the impact of pregnancy on clinical features and prognosis of breast cancer.

METHODS:

A single‐institution retrospective chart review was performed of 99 patients identified with PABC between 1992 and 2007. Non‐PABC controls were matched 2:1 to PABC cases by year of diagnosis and age. The differences in clinical features were compared between cases and controls using chi‐square tests. Univariate and multivariate analyses were performed to assess the effect of PABC on survival.

RESULTS:

Of the 99 PABC cases, breast cancer was diagnosed during pregnancy in 36 patients, and after delivery in 63. PABC cases were more likely than controls to be negative for estrogen receptor (59% vs 31%, P < .0001) and negative for progesterone receptor (72% vs 40%, P < .0001). Cases were also more likely to have advanced T class (P = .0271) and N class (P = .0104) and higher grade tumors (P = .0115). With a median follow‐up of 6.3 years for cases and 4.7 years for controls, overall survival did not differ between cases and controls (P = .0787). On multivariate analysis, the independent prognostic factors for overall survival were estrogen receptor status (P = .0031) and N class (P = .0003). The diagnosis of PABC was not an independent prognostic factor (P = .1317).

CONCLUSIONS:

PABC is associated with more adverse tumor features than non‐PABC matched for age and year of diagnosis. After correcting for pathologic features, the diagnosis of PABC is not in itself an adverse prognostic factor for survival. Cancer 2011. © 2011 American Cancer Society.     

Tumor characteristics and prognosis in women with pregnancy‐associated breast cancer

There is evidence of poor prognosis in women with pregnancy‐associated breast cancer (PABC) diagnosed during pregnancy or within 2 years of delivery. Using a large, population‐based cohort, we examined clinicopathologic features and survival in women with PABC. A cohort of women diagnosed with invasive breast cancer between 1992 and 2009 at ages 15–44 years was identified in the Swedish Cancer Register and the Breast Cancer Quality Registers. Dates of childbirths for each woman were retrieved from the Swedish Multi‐Generation Register. Age‐standardized distributions of tumor stage (tumor size, nodal status, metastasis), Elston grade and ER/PR/HER2 status were compared between nulliparous women and women with breast cancer during pregnancy and up to 10 years postdelivery. Adjusted hazard ratios for all‐cause mortality rates among patients were estimated using Cox regression. We identified 1,661 nulliparous women with breast cancer, 778 women with PABC (97 during pregnancy, 270 within first and 411 within second year postdelivery) and 3,598 during 2–10 years postdelivery. Compared to nulliparous women, women with PABC, and especially women diagnosed 0–12 months after delivery, had more advanced T and N stage, and higher proportions of ER/PR negative, HER2 positive and triple‐negative tumors. Increased hazard ratios were observed in women diagnosed within 5 years of delivery after adjustment for age, year, education and region. Following additional adjustment for tumor characteristics, the hazard ratios were attenuated and nonsignificant. The poorer prognosis observed in women with PABC appears to be largely explained by more adverse tumor characteristics at diagnosis.     

Prognosis of breast cancer diagnosed during pregnancy and early postpartum according to immunohistochemical subtype: A matched case–control study

Purpose

Pregnancy-associated breast cancer (PABC) poses a clinical challenge and its prognosis remains controversial. During the pregnancy and postpartum periods, the breast undergoes biological events that may uniquely influence disease behavior and treatment response. This study aimed to assess if a PABC diagnosis influences survival compared to non-PABC.

Methods

A single-center record review was performed to identify PABC patients diagnosed from January 2007 through June 2018. Two controls were matched to each PABC case by stage, immunohistochemical (IHC) subtype, age (±?3) and year of diagnosis (±?2). Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan–Meier method and compared with the log-rank test. Multivariate analysis was used to assess the impact of PABC on outcomes.

Results

125 PABC patients (pregnant: 62; postpartum: 63) and 250 controls were included. Median follow-up was 67.7 and 73.4 months, respectively. 4-year DFS was 62% in pregnant vs 78% in controls (p?=?0.010), and 63% in postpartum vs 83% in controls (p?=?0.034). Subanalysis by IHC subtype revealed a significantly inferior DFS in PABC with hormone receptor-positive/HER2-negative (p?=?0.032) and HER2-positive disease (p?=?0.005) compared to corresponding non-PABC patients. 4-year OS was similar between case groups and controls. Multivariate analysis supported the independent impact of pregnant and postpartum status on DFS (p?<?0.05).

Conclusion

Patients diagnosed during pregnancy and early postpartum are at high risk of recurrence. Further research is warranted to better characterize PABC tumor biology and enable the identification of novel therapeutic interventions to improve treatment outcomes.

     

The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation

Physicians are often approached by young women with a BRCA mutation and a recent history of breast cancer who wish to have a baby. They wish to know if pregnancy impacts upon their future risks of cancer recurrence and survival. To date, there is little information on the survival experience of women who carry a mutation in one of the BRCA genes and who become pregnant. From an international multi-center cohort study of 12,084 women with a BRCA1 or BRCA2 mutation, we identified 128 case subjects who were diagnosed with breast cancer while pregnant or who became pregnant after a diagnosis of breast cancer. These women were age-matched to 269 mutation carriers with breast cancer who did not become pregnant (controls). Subjects were followed from the date of breast cancer diagnosis until the date of last follow-up or death from breast cancer. The Kaplan–Meier method was used to estimate 15-year survival rates. The hazard ratio for survival associated with pregnancy was calculated using a left-truncated Cox proportional hazard model, adjusting for other prognostic factors. Among women who were diagnosed with breast cancer when pregnant or who became pregnant thereafter, the 15-year survival rate was 91.5 %, compared to a survival of 88.6 % for women who did not become pregnant (adjusted hazard ratio = 0.76; 95 % CI 0.31–1.91; p = 0.56). Pregnancy concurrent with or after a diagnosis of breast cancer does not appear to adversely affect survival among BRCA1/2 mutation carriers.     

Impact of hospital volume on breast cancer outcome: a population-based study in the Netherlands

For low-volume tumours, high surgical hospital volume is associated with better survival. For high-volume tumours like breast cancer, this association is unclear. The aim of this study is to determine to what extent the yearly surgical hospital breast cancer volume is associated with overall survival. All patients, diagnosed with primary invasive non-metastatic breast cancer in the period 2001–2005, were selected from the Netherlands Cancer Registry. Hospitals were grouped by their annual volume of surgery for invasive breast cancer. Cox proportional hazard models were used including patient and tumour characteristics as covariates. Follow-up was completed until the 1st of February 2013. Primary endpoint was 10-year overall survival rate. In total, 58,982 patients with invasive non-metastatic breast cancer were diagnosed during the period 2001–2005. Hospitals were grouped by their (mean) annual surgical volume: <75 (n = 19), 75–99 (n = 30), 100–149 (n = 29), 150–199 (n = 9) and ≥200 (n = 14). The 10-year observed survival rates were 77, 81, 80, 82 and 82 %, respectively. After case-mix adjustment, patients in low-volume hospitals had a HR of 1.09 (<75 vs. ≥200; 95 % CI 1.03–1.15). Survival was significantly higher for lobular carcinoma and for diagnosis in the most recent year (2005). Being a male, having a higher age at diagnosis, a higher tumour grade, a larger tumour size, a higher number of positive lymph nodes, an earlier year of diagnosis and a lower SES resulted in a reduced survival and influenced death, all to a larger extent than surgical volume did. In the Netherlands, surgical hospital volume influences 10-year overall survival only marginally and far less than patient and tumour characteristics. No difference in survival was revealed for invasive non-metastatic breast cancer patients in hospitals with 75–99 operations per year compared with hospitals with over 200 operations per year.     

Trajectory of overall health from self-report and factors contributing to health declines among cancer survivors

Purpose

This study aims to quantify trajectories of overall health pre- and post-diagnosis of cancer, trajectories of overall health among cancer-free individuals, and factors affecting overall health status.

Methods

Overall health status, derived from self-rated health report, of Atherosclerosis Risk in Communities cohort participants diagnosed with incident cancer [lung (n = 400), breast (n = 522), prostate (n = 615), colorectal (n = 303)], and cancer-free participants (n = 11,634) over 19 years was examined. Overall health was evaluated in two ways: (1) overall health was assessed until death or follow-up year 19 (survivorship model) and (2) same as survivorship model except that a self-rated health value of zero was used for assessments after death to follow-up year 19 (cohort model). Mean overall health at discrete times was used to generate overall health trajectories. Differences in repeated measures of overall health were assessed using linear growth models.

Results

Overall health trajectories declined dramatically within one-year of cancer diagnosis. Lung, breast, and colorectal cancer were associated with a significant decreased overall health score (β) compared to the cancer-free group (survivorship model: lung—7.00, breast—3.97, colorectal—2.12; cohort model: lung—7.63, breast—5.07, colorectal—2.30). Other predictors of decreased overall health score included low education, diabetes, cardiovascular disease, and age.

Conclusions

All incident cancer groups had declines in overall health during the first year post-diagnosis, which could be due to cancer diagnosis or intensive treatments. Targeting factors related to overall health declines could improve health outcomes for cancer patients.     

Breast cancer subtype and survival by parity and time since last birth

Background

Pregnancy affects breast cancer risk but how it affects the subtype and prognosis remain controversial. We studied the effect of parity and time since last birth on breast cancer subtype and outcome.

Patients and methods

We conducted a retrospective multivariate cohort study including all premenopausal women with early breast cancer aged ≤ 50 years (N = 1306) at diagnosis at the University Hospitals Leuven (Jan. 2000–Dec. 2009). Primary study endpoints were the breast cancer subtype, disease-free survival, and distant disease-free survival by parity and time since last birth. Statistical methods used were baseline-category logits models and Cox proportional hazard models. Multivariable models were used to correct for possible confounders.

Results

Breast cancer subtypes did not differ between nulliparous (N = 266) and parous women (N = 1040) but subtypes differed significantly in parous women by time since last birth (p < 0.001). Tumors within 5 years of last birth were proportionally more likely triple negative and HER-2 like, even when corrected for age at diagnosis. After a mean follow-up period of 10 years, parous women had a better disease-free survival compared to nulliparous women (HR 0.733; CI 0.560–0.961; p = 0.025, HR 0.738; CI 0.559–0.974; p = 0.032 before and after correction for known prognostic factors, respectively). In parous women, a longer time since last birth was correlated with a longer disease-free survival compared to patients with a recent pregnancy (HR 0.976; CI 0.957–0.996; p = 0.018). However, after correction, this association completely disappeared (HR 1.010; CI 0.982–1.040; p = 0.480).

Conclusion

We observed a better disease-free survival for parous than nulliparous women. The influence of recent birth on disease-free survival is probably due to tumor and patient characteristics, as recent birth is associated with more aggressive subtypes.

     

Impact of recent parity on histopathological tumor features and breast cancer outcome in premenopausal Japanese women

Although previous studies have reported that onset at young age is associated with poor prognosis in breast cancer, the correlation between reproductive factors, breast cancer characteristics, and prognosis remains unclear. Five hundred and twenty-six premenopausal young women diagnosed with primary invasive breast cancer between January 2000 and December 2007 were included in this study. Patients were classified into four groups according to their reproductive history: women who gave birth within the previous 2 years (group A), women who gave birth between 3 and 5 years previously (group B), women who gave birth more than 5 years previously (group C), and nulliparous women (group N). The correlation between the time since last childbirth to diagnosis, histopathological tumor features, and breast cancer prognosis was evaluated. Breast cancer patients who had given birth more recently had more advanced stage tumors; larger sized tumors; a higher rate of axillary lymph node metastases; a higher histological tumor grade; and increased progesterone receptor (PgR)?, HER2+, and triple negative tumors than patients who had given birth less recently or not at all. Group A patients had significantly shorter survival times than patients in both groups C and N (log rank test; p < 0.001). After adjusting for tumor characteristics, the hazard ratio for death in group A was 2.19 compared with group N (p = 0.036), and the adjusted hazard ratio restricted to patients in group A with hormone-receptor-positive, and HER2? tumors was 3.07 (p = 0.011). Young breast cancer patients who had given birth more recently had tumors with more aggressive features and worse prognoses compared with patients who had given birth less recently or were nulliparous.     

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.     

Serum 25-hydroxyvitamin D at pregnancy and risk of breast cancer in a prospective study

BackgroundSeveral laboratory and epidemiological studies have inversely linked endogenous vitamin D and the risk of breast cancer. The acquisition of vitamin D over time on the relative risk (RR) of the disease development is not known. In a longitudinal study, we evaluated the association between vitamin D levels at pregnancy over time with the risk of breast cancer, and pregnancy-associated breast cancer.MethodThe risk for subsequent development of breast cancer associated with serum 25-hydroxyvitamin (25-OHD) levels was assessed for consecutive (1st and 2nd pregnancy) samples of 100 cases, with mean lag times (μ_t) of 7.4 and 4.6 years between sampling and the diagnosis, and matched (parity, age, year, season) controls. Pregnancy-associated breast cancer (PABC, 111 case–control pairs, μ_t = 1year) risk was also studied. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the lowest quintile as the reference.ResultsSerum 25-OHD level was not associated with an increased risk neither at the 1st nor at the 2nd pregnancy samples (OR = 1.4, 95%CI 0.6–3.4; OR 1.4, 95%CI 0.7–2.8, respectively), but was associated with an increased risk of PABC (OR = 2.7, 95%CI 1.04–6.7).ConclusionGenerally, vitamin D may not be related to breast cancer risk but the increased PABC risk fits the association of vitamin D with the most aggressive cancers, and warrants caution with vitamin D supplementation during pregnancy.     

Impact of full-field digital mammography on pre-operative diagnosis and surgical treatment of mammographic microcalcification

Accurate pre-operative diagnosis of impalpable breast lesions correlates closely with the number of surgical procedures required for treatment. Correct diagnosis of mammographic microcalcification (MM) as ductal carcinoma in situ (DCIS) or invasive breast cancer is important because lesions upgraded to malignant diagnosis at surgery require repeat surgical procedures in 44 % of cases. Despite correct pre-operative diagnosis of MM, 26 % require second therapeutic operations to achieve surgical clearance. Theoretically, improved conspicuity of malignant MM using digital mammography could improve diagnostic work-up and improve surgical outcomes for MM. To determine the impact of full-field digital mammography (FFDM) on the diagnostic accuracy and positive predictive value (PPV) of biopsy of MM and surgical management of MM, screening and symptomatic cases with MM (n = 1,479) were reviewed for women imaged between August 2007 and March 2010 using screen-film mammography (SFM) (n = 711), and using FFDM, imaged between April 2010 to March 2012 (n = 768). Demographic information including pre and postoperative diagnosis, and number and types of surgical procedures were recorded. Overall, 302 (128 invasive) and 251 (110 invasive) malignant lesions were diagnosed using SFM and FFDM, respectively. Reduction in PPV of biopsy was observed (SFM 42.5 %; FFDM 32.7 %, p < 0.001). Correct pre-operative diagnosis was achieved at first attempt more often with FFDM (SFM 80.6 %; FFDM 89.5 %, p < 0.001). For lesions with pre-operative diagnosis, B5 more cases achieved surgical clearance with a single therapeutic operation with FFDM (SFM 66.3 %; FFDM 76.7 %, p = 0.017), and more lesions over 2 cm underwent mastectomy as the initial surgical procedure (SFM 47.0 %; FFDM 62.9 %, p = 0.005). Correct pre-operative diagnosis of MM using digital mammography reduced second therapeutic operations but increased mastectomy rate in larger cancers over two centimetres. This will increase concerns about treatment of lesions detected in the screening programme with widespread use of digital mammography.     

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.     

Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy

Women with BRCA1 and BRCA2 mutations have an elevated risk of breast cancer and ovarian cancer, but also of developing second primary breast cancer. BRCA1/2 mutation carriers with breast cancer must choose between breast conservation (BCT) and mastectomy (M) yet data on outcomes are limited. The purpose of this study is to compare long-term outcome following BCT and M in BRCA1/2 carriers. 655 women with BRCA1/2 mutations diagnosed with breast cancer and treated with BCT (n = 302) or M (n = 353) were identified and underwent follow-up to assess local, regional, and systemic recurrence. Local failure as first failure was significantly more likely in those treated with BCT compared to M, with a cumulative estimated risk of 23.5 vs. 5.5%, respectively, at 15 years (P < 0.0001); 15-year estimates in carriers treated with BCT and chemotherapy was 11.9% (P = 0.08 when compared to M). Most events appeared to be second primary cancers rather than failure to control the primary tumor. The risk of contralateral breast cancer was high in all groups, exceeding 40%, but was not statistically significantly different by use of adjuvant radiotherapy (RT) or not, suggesting no added risk from scatter RT at 10 and 15 years. There were no differences seen in regional or systemic recurrences between the BCT and M groups, and no difference in overall survival. In conclusion, BRCA1/2 mutation carriers with breast cancer have similar survival whether treated with M or BCT. However, women undergoing BCT have an elevated risk of a second in-breast event that is significantly reduced in the presence of chemotherapy. Contralateral breast cancer events are very common.     

Reproductive factors and risk of premenopausal breast cancer by age at diagnosis: Are there differences before and after age 40?

We examined the relationship between reproductive factors and risk of premenopausal breast cancer among women less than age 40 compared with older premenopausal women. We documented 374 incident cases of breast cancer diagnosed before age 40, and 2,533 cases diagnosed at age 40 and older among premenopausal women in the Nurses’ Health Study cohorts. Biennial questionnaires were used to determine age at menarche, age at first birth, parity, breastfeeding, and other reproductive factors. Multivariate relative risks (RR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models within age at diagnosis groups. Tumors in younger women were significantly more likely to be higher grade, larger size, and hormone receptor negative than were tumors in older premenopausal women (p < 0.0001). There was no significant heterogeneity according to age in associations between reproductive factors and risk of premenopausal breast cancer. First birth at age 30 or older increased breast cancer risk in both age groups (age <40: RR 1.10, 95 % CI 0.80–1.50; age ≥40: RR 1.16, 95 % CI 1.02–1.32; p-heterogeneity = 0.44). Risk of premenopausal breast cancer decreased with each additional year of age at menarche in both age groups (age <40: RR 0.93, 95 % CI 0.87–0.99; p trend = 0.02; age ≥40: RR 0.94, 95 % CI 0.91–0.97; p trend = <0.0001). Among premenopausal parous women, breastfeeding was protective regardless of age at diagnosis (age <40: RR 0.84, 95 % CI 0.57–1.22; age ≥40: RR 0.85, 95 % CI 0.72–0.99; p-heterogeneity = 0.79). In the largest prospective examination of reproductive risk factors and risk of breast cancer before and after age 40, we found that younger women were more likely to develop tumors with less favorable prognostic characteristics. However, associations between reproductive factors and risk of breast cancer were similar regardless of age at diagnosis of premenopausal breast cancer.     

35例妊娠期乳腺癌临床病理特征及预后分析

目的 通过与非妊娠期乳腺癌（non-PABC）比较分析妊娠是否影响妊娠期乳腺癌（PABC）患者的生存。方法 回顾性分析PABC患者资料,对PABC病例按TNM分期、分子分型、发病年龄和诊断时年份与non-PABC病例进行1:2配对。Kaplan-Meier法分析无病生存期（DFS）和总生存期（OS）,Log rank检验进行比较。Cox多因素分析评估影响PABC预后的危险因素。结果 PABC组纳入35例患者（妊娠10例;产后一年内25例）,non-PABC组纳入70例患者。中位随访时间分别为68.5和70.7月。PABC组5年DFS为51.6%,non-PABC组为72.8%（χ²=4.72, P=0.029）;PABC组和non-PABC的5年OS相似（χ²=1.769, P=0.183）。Cox多因素分析显示妊娠是影响PABC患者DFS的独立危险因素（P=0.011）。结论 妊娠期乳腺癌复发风险高,有必要通过进一步研究以便更早期发现妊娠期乳腺癌,并采取干预措施来提高治疗效果。     

Aromatase inhibitors in obese breast cancer patients are not associated with increased plasma estradiol levels

Obesity, in postmenopausal women, has been associated to a higher breast cancer incidence and worst prognosis. Some studies suggested a decrease in aromatase inhibitors (AI) efficacy in obese postmenopausal breast cancer patients, although estradiol levels were not measured. The purpose of the present study was to verify if estradiol levels are measurable in postmenopausal women under AI. If achievable, the goal is to compare the estradiol levels in lean versus obese postmenopausal women under AI treatment for non-metastatic breast cancer. Postmenopausal women were recruited in accordance to one of these four groups: lean [body mass index (BMI) of 18–25 kg/m²] under AI (n = 30), obese (BMI ≥30 kg/m²) under AI (n = 30), lean AI-naïve (n = 10), and obese AI-naïve (n = 10). Lean and obese women were matched according to their age. Estradiol levels were measured in plasma using an ELISA. The Wilcoxon signed-rank test was used to assess the significance of the differences between the groups. Estradiol levels in postmenopausal women under AI varied from 0 to 94.65 pg/ml with a median value of 0.98 pg/ml. Obese AI-naïve women had higher estradiol levels than lean AI-naïve women (p = 0.03). There was no difference in estradiol levels between lean and obese women under AI (p = 0.76). Despite very low plasma levels, it is possible to measure the estradiol levels in postmenopausal women under AI treatment. Our results suggest that the known impact of obesity on recurrence risk in women under AI treatment may not be due to incomplete aromatase inhibition. Further works are needed to examine closely the aromatase-independent pathways that are linking obesity to breast cancer risk and recurrence.