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.     

Clinical subtypes and prognosis of pregnancy-associated breast cancer: results from the Korean Breast Cancer Society Registry database

Purpose

We analyzed the clinicopathologic characteristics and prognosis of pregnancy-associated breast cancer (PABC) according to clinical subtypes to better understand the characteristics of PABC.

Methods

A total of 83,792 female patients between the ages of 20 and 49 were enrolled in the Korean Breast Cancer Society Registry database from January 1, 1996 to December 31, 2015. ‘PABC’ is defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. Other patients were defined as ‘non-PABC’ patients.

Results

In non-PABC patients, luminal A subtype was the most common (50.2%). In PABC patients, TNBC was the most common (40.4%) subtype, while luminal A comprised 21.2% and HER2 subtype comprised 17.3%. There was a significant difference in overall survival (OS). In non-PABC patients, TNBC had the highest HR (HR 2.3, 95% CI 2.1–2.6). In PABC patients, the luminal B subtype (HR+ HER2-high Ki67) had the highest HR at 7.0 (95% CI 1.7–29.1). In multivariate analysis of OS by subtypes, PABC patients had significantly higher HR than non-PABC patients in the HER2 subtype (HR 2.0, 95% CI 1.1–3.7) and luminal B subtype (HR+ HER2-high Ki67) (HR 4.4, 95% CI 1.6–12.3).

Conclusion

PABC showed different biologic features than non-PABC. PABC had a particularly poor prognosis in the luminal B (HR+ HER2-highKi67) and HER2 subtypes. To improve the prognosis of PABC, treatment should be considered according to subtype. Development of drugs that can be used during pregnancy is needed.

     

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。     

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.     

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.     

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.     

Active smoking and survival following breast cancer among African American and non-African American women in the Carolina Breast Cancer Study

Purpose

To examine racial differences in smoking rates at the time of breast cancer diagnosis and subsequent survival among African American and non-African American women in the Carolina Breast Cancer Study (Phases I/II), a large population-based North Carolina study.

Methods

We interviewed 788 African American and 1,020 Caucasian/non-African American women diagnosed with invasive breast cancer from 1993 to 2000, to assess smoking history. After a median follow-up of 13.56 years, we identified 717 deaths using the National Death Index; 427 were breast cancer-related. We used Cox regression to examine associations between self-reported measures of smoking and breast cancer-specific survival within 5 years and up to 18 years after diagnosis conditional on 5-year survival. We examined race and estrogen receptor status as potential modifiers.

Results

Current (vs never) smoking was not associated with 5-year survival; however, risk of 13 year conditional breast cancer-specific mortality was elevated among women who were current smokers at diagnosis (HR 1.54, 95% CI 1.06–2.25), compared to never smokers. Although smoking rates were similar among African American (22.0%) and non-African American (22.1%) women, risk of breast cancer-specific mortality was elevated among African American (HR 1.69, 95% CI 1.00–2.85), but only weakly elevated among non-African American (HR 1.22, 95% CI 0.70–2.14) current (vs. never) smokers (P _Interaction = 0.30). Risk of breast cancer-specific mortality was also elevated among current (vs never) smokers diagnosed with ER^? (HR 2.58, 95% CI 1.35–4.93), but not ER⁺ (HR 1.11, 95% CI 0.69–1.78) tumors (P _Interaction = 0.17).

Conclusions

Smoking may negatively impact long-term survival following breast cancer. Racial differences in long-term survival, as related to smoking, may be driven by ER status, rather than by differences in smoking patterns.

     

Racial disparities in initiation of adjuvant endocrine therapy of early breast cancer

Endocrine therapy (ET) is the cornerstone of adjuvant therapy for hormone-receptor positive (HR+) breast cancer. The survival gap between African-American (AA) and white women with breast cancer is most pronounced in HR+ subtypes, and could be related to differences in ET use. The relationship between race and initiation of ET is not well defined. We investigated patterns of ET initiation by race in a diverse cohort of women covered by commercial health insurance. We identified 2,640 women with incident HR+ breast cancer in the North Carolina Central Cancer Registry whose records linked to commercial insurance claims using the Integrated Cancer Information and Surveillance System (ICISS) database. The sample included women age <65 years diagnosed with stage I–III HR+ cancers between 2004 and 2009. We used multivariate Poisson regression to examine the effect of race on likelihood of initiating ET. 14 % of women did not initiate ET within 12 months of diagnosis. AA women were 17 % less likely to initiate ET than whites (aRR 0.83, 95 % CI 0.74–0.93). When analyzed by subset, racial disparities persisted among women who received chemotherapy (aHR 0.67, 95 % CI 0.56–0.80) but not among women who did not receive chemotherapy (aHR 0.96, 95 % CI 0.76–1.21). AA women in our sample were less likely to initiate ET than whites, and this disparity was concentrated among chemotherapy-treated women. ET under-utilization may contribute to the racial survival gap in HR+ breast cancer, and represents an opportunity for intervention to reduce breast cancer disparities.     

Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population

Purpose

Many studies suggest increased body mass index (BMI) is associated with worse breast cancer outcomes, but few account for variability in screening, access to treatment, and tumor differences. We examined the association between BMI and risk of breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality, and evaluated whether tumor characteristics differ by BMI among a mammographically screened population with access to treatment.

Methods

Using a retrospective cohort study design, we followed 485 women aged ≥40 years diagnosed with stage I/II breast cancer within 24 months of a screening mammogram occurring between 1988 and 1993 for 10-year outcomes. BMI before diagnosis was categorized as normal (<25 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²). Tumor marker expression was assessed via immunohistochemistry using tissue collected before adjuvant treatment. Medical records were abstracted to identify treatment, recurrence, and mortality. We used Cox proportional hazards to separately model the hazard ratios (HR) of our three outcomes by BMI while adjusting for age, stage, and tamoxifen use.

Results

Relative to normal-weight women, obese women experienced increased risk of recurrence (HR 2.43; 95 % CI 1.34–4.41) and breast cancer death (HR 2.41; 95 % CI 1.00–5.81) within 10 years of diagnosis. There was no association between BMI and all-cause mortality. Obese women had significantly faster growing tumors, as measured by Ki-67.

Conclusions

Our findings add to the growing evidence that obesity may contribute to poorer breast cancer outcomes, and also suggest that increased tumor proliferation among obese women is a pathway that explains part of their excess risk of adverse outcomes.     

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.     

The effect of atmospheric particulate matter on survival of breast cancer among US females

Short-term effects of ambient particulate matter (PM) on cardiopulmonary morbidity and mortality have been consistently documented. However, no study has investigated its long-term effects on breast cancer survival. We selected all female breast cancer cases (n = 255,128) available in the California Surveillance Epidemiology and End Results cancer data. These cases were linked to 1999–2009 California county-level PM daily monitoring data. We examined the effect of PM on breast cancer survival. Results from Kaplan–Meier survival analysis show that female breast cancer cases living in areas with higher levels of PM₁₀ and PM_2.5 had a significant shorter survival than those living in areas with lower exposures (p < 0.0001). The results from marginal cox proportional hazards models suggest that exposure to higher PM₁₀ (HR 1.13, 95 % CI 1.02–1.25, per 10 μg/m³) or PM_2.5 (HR 1.86, 95 % CI 1.12–3.10, per 5 μg/m³) was significantly associated with early mortality among female breast cancer cases after adjusting for individual-level covariates such as demographic factors, cancer stage and year diagnosed, and county-level covariates such as socioeconomic status and accessibility to medical resources. Interactions between cancer stage and PM were also observed; the effect of PM on survival was more pronounced among individuals diagnosed with early stage cancers. This study suggests that exposure to high levels of PM may have deleterious effects on the length of survival from breast cancer, particularly among women diagnosed with early stage cancers. The findings from this study warrant further investigation.     

Long-term surveillance mammography and mortality in older women with a history of early stage invasive breast cancer

Annual surveillance mammograms in older long-term breast cancer survivors are recommended, but this recommendation is based on little evidence and with no guidelines on when to stop. Surveillance mammograms should decrease breast cancer mortality by detecting second breast cancer events at an earlier stage. We examined the association between surveillance mammography beyond 5 years after diagnosis on breast cancer-specific mortality in a cohort of women aged ≥65 years diagnosed 1990–1994 with early stage breast cancer. Our cohort included women who survived disease free for ≥5 years (N = 1,235) and were followed from year 6 through death, disenrollment, or 15 years after diagnosis. Asymptomatic surveillance mammograms were ascertained through medical record review. We used Cox proportional hazards regression stratified by follow-up year to calculate the association between time-varying surveillance mammography and breast cancer-specific and other-than-breast mortality adjusting for site, stage, primary surgery type, age and time-varying Charlson Comorbidity Index. The majority (85 %) of the 1,235 5-year breast cancer survivors received ≥1 surveillance mammogram in years 5–9 (yearly proportions ranged from 48 to 58 %); 82 % of women received ≥1 surveillance mammogram in years 10–14. A total of 120 women died of breast cancer and 393 women died from other causes (average follow-up 7.3 years). Multivariable models and lasagna plots suggested a modest reduction in breast cancer-specific mortality with surveillance mammogram receipt in the preceding year (IRR 0.82, 95 % CI 0.56–1.19, p = 0.29); the association with other-cause mortality was 0.95 (95 % CI 0.78–1.17, p = 0.64). Among older breast cancer survivors, surveillance mammography may reduce breast cancer-specific mortality even after 5 years of disease-free survival. Continuing surveillance mammography in older breast cancer survivors likely requires physician–patient discussions similar to those recommended for screening, taking into account comorbid conditions and life-expectancy.     

No association between low-dose aspirin use and breast cancer outcomes overall: a Swedish population-based study

Background

Results from previous studies indicate that use of low-dose aspirin may improve breast cancer prognosis. We evaluated aspirin use and breast cancer outcomes in relation to clinical characteristics as well as dose and duration of aspirin use.

Methods

We used information from the Regional Breast Cancer Quality-of-Care Registries in three Swedish regions to identify 21,414 women diagnosed with a first stage I–III breast cancer between 1 April 2006 and 31 December 2012. The cohort was further linked to nationwide registers to retrieve information about dispensing low-dose aspirin before and after breast cancer diagnosis, comorbidity and causes of death. In a separate analysis, we investigated time to breast cancer death among 621 women with stage IV disease at diagnosis. Associations were evaluated using a multivariable Cox proportional hazards model.

Results

Among women with stage I–III breast cancer, 2660 (12.4%) used low-dose aspirin shortly before breast cancer diagnosis and 4091 (19.1%) were users during follow-up. Women were followed for a median of 3.8 years after diagnosis. There was no association between aspirin use and breast cancer-specific death in multivariable analyses (use before diagnosis: hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.77–1.12; use after diagnosis: HR 1.00, 95% CI 0.74–1.37). Similarly, aspirin use was not associated with risk of first recurrence/metastases in a subgroup of stage I–III breast cancer patients (HR 0.97, 95% CI 0.86–1.10). However, in analyses stratified by stage, an inverse association between low-dose aspirin use after diagnosis and breast cancer death was found for women with stage I tumors (HR 0.53, 95% CI 0.29–0.96). Among women with stage IV disease at diagnosis, aspirin use was not associated with time to breast cancer death (HR 0.91, 95% CI 0.67–1.23).

Conclusion

In this large population-based cohort study there was no evidence that low-dose aspirin use before or after breast cancer diagnosis is associated with a reduced risk of adverse outcomes overall in breast cancer. However, a potential benefit was noted among women with stage I tumors, warranting further investigation.

     

Mortality outcome among medically underserved women screened through a publicly funded breast cancer control program, 1997–2007

Purpose

The purpose of this study was to assess treatment and mortality differences between women diagnosed with breast cancer through Nebraska’s Every Woman Matters (EWM) program and women diagnosed through other sources.

Methods

A retrospective analysis was performed using 10 years of Nebraska Cancer Registry and EWM program data on women aged 40–74 years. This study used chi-square and multivariate logistic regression with mortality as the outcome of interest.

Results

From 1997 to 2007, 4,739 women were diagnosed with breast cancer, 435 (9.1 %) of whom were diagnosed through EWM. The EWM and non-EWM groups differed significantly in age, race, marital status, location of residence at the time of diagnosis, neighborhood poverty level at the time of diagnosis, tumor stage at diagnosis, and chemotherapy. No significant differences were found between the two groups in radiation therapy, surgical resection, and hormone therapy. In both 1- and 5-year multivariate mortality models, the odds of dying for those in the EWM program were not statistically significantly different from the odds of dying for those not in the EWM program. In the 1-year mortality model, residents of urban metropolitan counties (OR 2.079; 95 % CI 1.663–2.598) had an increased odds of dying compared to residents of rural counties. In the 5-year mortality model, black women (OR 2.239; 95 % CI 1.453–3.450), residents of areas with a high (more than 20 %) neighborhood poverty level at the time of diagnosis (OR 1.589; 95 % CI 1.204–2.097), and unmarried women (OR 1.334; 95 % CI 1.164–1.528) had higher odds of death. Both groups have received similar treatments.

Conclusions

Targeted outreach to vulnerable groups for cancer screening may improve cancer outcomes and reduce disparities.     

Inferior survival for young patients with contralateral compared to unilateral breast cancer: a nationwide population-based study in the Netherlands

To compare overall survival between women with unilateral breast cancer (UBC) and contralateral breast cancer (CBC). Women with UBC (N = 182,562; 95 %) and CBC (N = 8,912; 5 %) recorded in the Netherlands Cancer Registry between 1989 and 2008 were included and followed until 2010. We incorporated CBC as a time-dependent covariate to compute the overall mortality rate ratio between women with CBC and UBC. Prognostic factors for overall death were examined according to age at first breast cancer. Women with CBC exhibited a 30 % increase in overall mortality (Hazard Ratio (HR), 95 % Confidence Interval: 1.3, 1.3–1.4) compared with UBC, decreasing with rising age at diagnosis of first breast cancer (<50 years: 2.3, 2.2–2.5 vs. ≥70 years: 1.1, 1.0–1.1). Women older than 50 years at CBC diagnosis and diagnosed 2–5 years after their first breast cancer exhibited a 20 % higher death risk (1.2, 1.0–1.3) compared to those diagnosed within the first 2 years. In women younger than 50 years, the HR was significantly lower if the CBC was diagnosed >5 years after the first breast cancer (0.7, 0.5–0.9). The prognosis for women with CBC significantly improved over time (2004–2008: 0.6, 0.5-0.7 vs. 1989–1993). Women with CBC had a lower survival compared to women with UBC, especially those younger than 50 years at first breast cancer diagnosis. A tailored follow-up strategy beyond current recommendations is needed for these patients who, because of their age and absence of known familial risk, are currently not invited for population-based screening.     

Pregnancy during breast cancer: does a mother’s parity status modify an offspring’s mortality risk?

To assess whether children born to primiparous women around the time of a breast cancer diagnosis have an increased mortality risk. From the merged Swedish Multi-Generation and Cancer Registers, we identified 49,750 eligible children whose mother was diagnosed with breast cancer between 1958 and 2010. Mortality rates in offspring were compared to the background population using standardized mortality ratios (SMR), adjusted for calendar year of birth, attained age, and sex, and calculated for each category of timing of delivery (before, around, or after mother’s diagnosis) and mother’s parity status. Hazard ratios were assessed using a Cox proportional hazards model and adjusted for socioeconomic status, year of birth and mother’s age at birth. Children born to a primiparous woman around a breast cancer diagnosis had a mortality rate five times greater than the background population (SMR 5.26, 95 % CI 1.93–11.5), whereas children born to a multiparous woman had a twofold increase (SMR 2.40, 95 % CI 1.10–4.55). Children of primiparous women born around diagnosis had an adjusted hazard ratio fourfold to that of children of primiparous women born before their mother’s diagnosis (HR 4.29, 95 % CI 1.68–8.91), whereas hazard ratios for children of primiparous or multiparous women born at other times were not statistically significant. Children born to primiparous women around a breast cancer diagnosis have an increased relative mortality risk. Although relative risk is increased, in absolute terms children born from a cancer complicated pregnancy do relatively well. Additional investigations are needed to elucidate the reason(s) underlying this observation before the information can be used to inform patient counseling and clinical care.     

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.

     

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.     

Multivitamin and mineral use and breast cancer mortality in older women with invasive breast cancer in the women’s health initiative

Multivitamin use is common in the United States. It is not known whether multivitamins with minerals supplements (MVM) used by women already diagnosed with invasive breast cancer would affect their breast cancer mortality risk. To determine prospectively the effects of MVM use on breast cancer mortality in postmenopausal women diagnosed with invasive breast cancer, a prospective cohort study was conducted of 7,728 women aged 50–79 at enrollment in the women’s health initiative (WHI) in 40 clinical sites across the United States diagnosed with incident invasive breast cancer during WHI and followed for a mean of 7.1 years after breast cancer diagnosis. Use of MVM supplements was assessed at WHI baseline visit and at visit closest to breast cancer diagnosis, obtained from vitamin pill bottles brought to clinic visit. Outcome was breast cancer mortality. Hazard ratios and 95 % confidence intervals (CIs) for breast cancer mortality comparing MVM users to non-users were estimated using Cox proportional hazard regression models. Analyses using propensity to take MVM were done to adjust for potential differences in characteristics of MVM users versus non-users. At baseline, 37.8 % of women reported MVM use. After mean post-diagnosis follow-up of 7.1 ± 4.1 (SD) years, there were 518 (6.7 %) deaths from breast cancer. In adjusted analyses, breast cancer mortality was 30 % lower in MVM users as compared to non-users (HR = 0.70; 95 % CI 0.55, 0.91). This association was highly robust and persisted after multiple adjustments for potential confounding variables and in propensity score matched analysis (HR = 0.76; 95 % CI 0.60–0.96). Postmenopausal women with invasive breast cancer using MVM had lower breast cancer mortality than non-users. The results suggest a possible role for daily MVM use in attenuating breast cancer mortality in women with invasive breast cancer but the findings require confirmation.