Mammographic breast density and the risk of breast cancer: A systematic review and meta-analysis

ObjectivesMammographic density is a well-defined risk factor for breast cancer and having extremely dense breast tissue is associated with a one-to six-fold increased risk of breast cancer. However, it is questioned whether this increased risk estimate is applicable to current breast density classification methods. Therefore, the aim of this study was to further investigate and clarify the association between mammographic density and breast cancer risk based on current literature.MethodsMedline, Embase and Web of Science were systematically searched for articles published since 2013, that used BI-RADS lexicon 5th edition and incorporated data on digital mammography. Crude and maximally confounder-adjusted data were pooled in odds ratios (ORs) using random-effects models. Heterogeneity regarding breast cancer risks were investigated using I² statistic, stratified and sensitivity analyses.ResultsNine observational studies were included. Having extremely dense breast tissue (BI-RADS density D) resulted in a 2.11-fold (95% CI 1.84–2.42) increased breast cancer risk compared to having scattered dense breast tissue (BI-RADS density B). Sensitivity analysis showed that when only using data that had adjusted for age and BMI, the breast cancer risk was 1.83-fold (95% CI 1.52–2.21) increased. Both results were statistically significant and homogenous.ConclusionsMammographic breast density BI-RADS D is associated with an approximately two-fold increased risk of breast cancer compared to having BI-RADS density B in general population women. This is a novel and lower risk estimate compared to previously reported and might be explained due to the use of digital mammography and BI-RADS lexicon 5th edition.     

The oncologic impact of hormone replacement therapy in premenopausal breast cancer survivors: A systematic review

SynopsisThis is the first systematic review to investigate the risk of recurrence in breast cancer survivors <50 years old who have used hormone replacement therapy (HRT).BackgroundThe risk of HRT in premenopausal breast cancer survivors is unclear. Due to the higher incidence of estrogen receptor negative tumours in women <50, the potential for HRT to promote breast cancer recurrence may differ from older age groups.MethodsWe performed a search of Medline, EMBASE and CINAHL through June 2016. For the observational studies relative risk (RR) and 95% confidence interval (CI) were calculated for the recurrence rate among HRT users and nonusers. A random effects model was used to estimate the combined RR using the Mantel-Haenszel method.ResultsFour papers satisfied our inclusion criteria. 3477 subjects were analyzed. On pooled meta-analysis of breast cancer recurrence in the observational studies, no significant association was found between HRT and risk of recurrence (RR 1.04 [95% CI 0.45, 2.41]). The randomized controlled trial (RCT) included found an increased risk of recurrence with HRT among women <50 (HR 1.56 [95% CI 1.1–2.2]). However, among women of all ages with an estrogen receptor negative tumour there was no significant difference in recurrence when compared to hormone receptor positive tumours (HR 1.15 [95% CI 0.7–1.8, p = 0.55]).DiscussionThis review on HRT in breast cancer survivors <50 revealed conflicting results between randomized and observational study data. Further studies are warranted to investigate the association between HRT and recurrence rates in younger breast cancer survivors.     

Differences in breast cancer risk after benign breast disease by type of screening diagnosis

IntroductionWe aimed to assess differences in breast cancer risk across benign breast disease diagnosed at prevalent or incident screens.Materials and methodsWe conducted a retrospective cohort study with data from 629,087 women participating in a long-standing population-based breast cancer screening program in Spain. Each benign breast disease was classified as non-proliferative, proliferative without atypia, or proliferative with atypia, and whether it was diagnosed in a prevalent or incident screen. We used partly conditional Cox hazard regression to estimate the adjusted hazard ratios of the risk of breast cancer.ResultsCompared with women without benign breast disease, the risk of breast cancer was significantly higher (p-value = 0.005) in women with benign breast disease diagnosed in an incident screen (aHR, 2.67; 95%CI: 2.24–3.19) than in those with benign breast disease diagnosed in a prevalent screen (aHR, 1.87; 95%CI: 1.57–2.24). The highest risk was found in women with a proliferative benign breast disease with atypia (aHR, 4.35; 95%CI: 2.09–9.08, and 3.35; 95%CI: 1.51–7.40 for those diagnosed at incident and prevalent screens, respectively), while the lowest was found in women with non-proliferative benign breast disease (aHR, 2.39; 95%CI: 1.95–2.93, and 1.63; 95%CI: 1.32–2.02 for those diagnosed at incident and prevalent screens, respectively).ConclusionOur study showed that the risk of breast cancer conferred by a benign breast disease differed according to type of screen (prevalent or incident). To our knowledge, this is the first study to analyse the impact of the screening type on benign breast disease prognosis.     

Predictors of breast cancer development in a high-risk population

BACKGROUND: The purpose of this study was to investigate the strongest predictors of breast cancer in a high-risk population and to increase our understanding of the possible interactions between risk factors. METHODS: The Women At Risk High-Risk Registry provided the study population. The variables of interest included age at enrollment, presence of lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia, family history of breast cancer, body mass index, and Gail scores (5-year high-risk > or =1.7%). Univariate and multivariate analyses were conducted with the Cox proportional hazards regression model and years of follow-up evaluation as the time scale. RESULTS: Out of 1553 high-risk women, 79 (5%) developed breast cancer during a median follow-up period of 5 years. Results from the multivariate Cox model demonstrated that FHBC (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.05-2.97), ADH (HR = 1.90; 95% CI, 1.16-3.13), LCIS (HR = 1.71; 95% CI, .99-2.95), and a body mass index > or =30 (HR = 2.22; 95% CI, 1.14-4.35) were statistically significant predictors of breast cancer within this high-risk population. CONCLUSIONS: These results support current literature showing the synergistic increase in risk for patients with ADH, LCIS, and a positive family history of breast cancer. Obesity was also a strong predictor of breast cancer risk, which suggests that there may be a potentiating effect of obesity on other risk factors. Obesity may represent a modifiable risk factor, providing women with an opportunity to reduce their risk with lifestyle modification. Women with a strong family history of breast cancer or a diagnosis of ADH or LCIS may benefit most from risk-reduction strategies, chemoprevention, and surveillance.     

Evidence from a BreastScreen cohort does not support a longer inter-screen interval in women who have no conventional risk factors for breast cancer

ObjectivesTo determine screening outcomes in women who have no recorded risk factors for breast cancer.MethodsA retrospective population-based cohort study included all 1,026,137 mammography screening episodes in 323,082 women attending the BreastScreen Western Australia (part of national biennial screening) program between July 2007 and June 2017. Cancer detection rates (CDR) and interval cancer rates (ICR) were calculated in screening episodes with no recorded risk factors for breast cancer versus at least one risk factor stratified by age. CDR was further stratified by timeliness of screening (<27 versus ≥27 months); ICR was stratified by breast density.ResultsAmongst 566,948 screens (55.3%) that had no recorded risk factors, 2347 (40.9%) screen-detected cancers were observed. In screens with no risk factors, CDR was 50 (95%CI 48–52) per 10,000 screens and ICR was 7.9 (95%CI 7.4–8.4) per 10,000 women-years, estimates that were lower than screens with at least one risk factor (CDR 83 (95%CI 80–86) per 10,000 screens, ICR 12.2 (95%CI 11.5–13.0) per 10,000 women-years). Compared to timely screens with risk factors, delayed screens with no risk factors had similar CDR across all age groups and a higher proportion of node positive cancers (26.1% vs 20.7%). ICR was lowest in screens that had no risk factors nor dense breasts in all age groups.ConclusionsMajority of screens had no recorded breast cancer risk factors, hence a substantial proportion of screen-detected cancers occur in these screening episodes. Our findings may not justify less frequent screening in women with no risk factors.     

Age- and treatment-related associations with health behavior change among breast cancer survivors

ObjectiveThe aim of this study was to identify demographic and treatment-related factors associated with health-promoting behavior changes after a breast cancer diagnosis. Changes in health behaviors were also evaluated according to weight, exercise, diet and alcohol consumption patterns before breast cancer diagnosis.Materials and methodsWe examined self-reported behavior changes among 1415 women diagnosed with breast cancer in the NIEHS Sister Study cohort. Women reported changes in exercising, eating healthy foods, maintaining a healthy body weight, drinking alcohol, smoking, getting enough sleep, spending time with family and friends, and participating in breast cancer awareness events.ResultsOn average, women were 3.7 years from their breast cancer diagnosis. Overall, 20–36% reported positive changes in exercise, eating healthy foods, maintaining a healthy weight, or alcohol consumption. However, 17% exercised less. With each 5-year increase in diagnosis age, women were 11–16% less likely to report positive change in each of these behaviors (OR = 0.84–0.89; p < 0.05), except alcohol consumption (OR = 0.97; CI: 0.81, 1.17). Women who underwent chemotherapy were more likely to report eating more healthy foods (OR = 1.47; 95% CI 1.16–1.86), drinking less alcohol (OR = 2.01; 95% CI: 1.01, 4.06), and sleeping enough (OR = 1.41; 95% CI: 1.04, 1.91). The majority of women (50–84%) reported no change in exercise, eating healthy foods, efforts to maintain a healthy weight, alcohol consumption, sleep patterns, or time spent with family or friends.ConclusionsMany women reported no change in cancer survivorship guideline-supported behaviors after diagnosis. Positive changes were more common among younger women or those who underwent chemotherapy.     

Radial bone density and breast cancer risk in white and African-American women

A number of different models for assessing individual risk of breast cancer use known risk factors such as age, age at menarche, age at first live birth, previous breast biopsies, and family history. High bone mass in white women is also associated with an increased breast cancer risk; however, bone mass as a risk factor has not been studied in African-American women. We conducted a case-control study to evaluate bone mineral density as a risk factor for breast cancer in white and African-American women. We recruited 221 women with newly diagnosed breast cancer from a comprehensive breast cancer center at a large university hospital, and 197 control women who were frequency matched for ethnicity and age. Odds ratios were based on proximal and distal radial bone density measured by peripheral bone densitometry (Norland pDEXA) and expressed as a standardized Z-score (age and ethnicity specific). Logistic regression models were fitted controlling for body mass index, menopausal status, age, and HRT use (ever/never and duration). With proximal bone density Z-score included in the model as a continuous variable, a one-unit increase in radial shaft bone density increased the risk of breast cancer by 25% (p=0.02). When proximal bone density Z-score was analyzed as a dichotomous variable (0, >0) the odds ratio was 1.98 (95% CI, 1.32 to 2.97); that is, having an above average proximal bone density (age-specific) doubles the risk of breast cancer. There were no significant interactions with, and no appreciable confounding effects by, other covariates. An above-average radial shaft Z-score is a significant risk factor for breast cancer in both white and African-American women. The present study extends the association between bone mass and breast cancer risk to African-Americans, and suggests another potential application for bone density testing.     

Risk of secondary malignancies after radiation therapy for breast cancer: Comprehensive results

GoalsTo assess risks of secondary malignancies in breast cancer patients who received radiation therapy compared to patients who did not.MethodsThe SEER database was used to identify females with a primary diagnosis of breast cancer as their first malignancy, during 1973–2008. We excluded patients with metastatic disease, age <18 years, no definitive surgical intervention, ipsilateral breast cancer recurrence, or who developed a secondary malignancy within 1 year of diagnosis. Standardized incidence ratios and absolute excess risk were calculated using SEER*Stat, version 8.2.1 and SAS, version 9.4.Principle resultsThere were 374,993 patients meeting the inclusion criteria, with 154,697 who received radiation therapy. With a median follow-up of 8.9 years, 13% of patients (49,867) developed a secondary malignancy. The rate of secondary malignancies was significantly greater than the endemic rate in breast cancer patients treated without radiation therapy, (O/E 1.2, 95% CI 1.19–1.22) and with radiation therapy (O/E 1.33, 95% CI 1.31–1.35). Approximately 3.4% of secondary malignancies were attributable to radiation therapy. The increased risk of secondary malignancies in breast cancer patients treated with radiation therapy compared to those without was significant regardless of age at breast cancer diagnosis (p < 0.01) and more pronounced with longer latency periods.ConclusionThere was an increased risk of secondary malignancies for breast cancer patients both with and without radiation therapy compared to the general population. There was an increased risk in specific sites for patients treated with radiation therapy. This risk was most evident in young patients and who had longer latency periods.     

The impact of young age at diagnosis (age <40 years) on prognosis varies by breast cancer subtype: A U.S. SEER database analysis

PurposeWomen under 40 years old are at increased risk for developing human epidermal growth factor receptor 2 (HER2) positive or triple negative subtype and more advanced breast cancer, yet young age itself has also historically been an independent prognostic factor.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) Program, we examined data for 271,173 women with stage I-III breast cancer between 2010 and 2015. Using Fine and Gray regression models to account for competing risks, we examined the risk of breast cancer-specific death by age and clinical subtypes, considering grade, hormone receptor (HR) and HER2 status, adjusting for demographic, clinical and treatment variables.ResultsOf 271,173 women eligible for analysis, 14,109 were <40 years of age. Women under 40 years old were more likely to be non-white, uninsured, and to have higher stage, higher grade, HER2-positive and triple-negative subtype disease (all, p < 0.001). Compared to women ages 40–60, women ages <40 had higher breast cancer mortality (hazard ratio, 1.8; 95% confidence interval (CI) 1.6–1.9) in unadjusted analysis. In models controlling for demographic, clinical and treatment factors, young age was significantly associated with an increased risk of breast cancer mortality among women with HR-positive, lower grade disease (hazard ratio 1.7; 95% CI 1.4–2.1) but not for women with high grade/HR-positive, HER2-positive, or triple-negative disease. Women age >75 had increased breast cancer mortality in all subtypes.ConclusionWith modern clinical subtyping, age under 40 remains independently associated with worse outcomes in 30 months follow-up only in HR-positive, lower grade disease.     

Statin use and patterns of breast cancer recurrence in the Malmö Diet and Cancer Study

BackgroundAccumulating evidence suggests that statins have a beneficial effect on breast cancer prognosis. Previous studies have reported a positive association between statin use and breast cancer survival; however, the relationship between statin use and patterns of breast cancer recurrence remains unclear.Patients and methodsWe identified all Malmö Diet and Cancer Study (MDCS) participants diagnosed with incident invasive breast cancer between 2005 and 2014. The follow-up period began at breast cancer diagnosis and continued until the first invasive breast cancer recurrence event, death, emigration or the end of the follow-up (June 8, 2020). We estimated incidence rates (IRs) of recurrence and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for disease recurrence to compare post-diagnosis statin users with non-users.ResultsThe final study cohort consisted of 360 eligible patients with a median follow-up of 8.6 years. Overall, there were 71 recurrences in 2932 total person-years. According to statin use, there were 14 recurrences in 595 person-years among statin users, and 57 recurrences in 2337 person-years in non-users. Statin use was associated with a reduced risk of breast cancer recurrence (HR_adj = 0.88 [95% CI: 0.82–0.96]). Regarding the pattern of recurrence, statin use was associated with a reduced risk of distant recurrence (HR_adj = 0.86 [95% CI: 0.80–0.94]) but not loco-regional recurrence (HR_adj = 0.97 [95% CI: 0.87–1.08]).ConclusionIn the MDCS, statin use was associated with a reduced risk of distant breast cancer recurrence, whereas no association between statin use and loco-regional breast cancer recurrence was found. This site-based difference in disease recurrence may be explained by statin's inhibition of epithelial-mesenchymal transition.     

Worry and risk perception of breast cancer in a prevention trial of low dose tamoxifen in midlife postmenopausal hormone users

ObjectiveThere is increasing interest in combining postmenopausal hormone therapy (HT) and SERMs in midlife women. We previously showed that refusal to participate in a prevention trial of low dose tamoxifen in HT users was associated with higher worry about breast cancer. Given this counterintuitive finding, we studied which factors influenced worry and risk perception of breast cancer.MethodsWe assessed the relationships of breast cancer worry and risk perception with age, age at menopause, Gail risk, education, adherence to mammographic screening, BMI, smoking, physical activity, alcohol use, anxiety and depression in 457 midlife HT users who were eligible to participate in the trial.ResultsWomen with menopause <48 years were more worried about breast cancer than women with menopause >52 years (OR = 5.0, 95% CI, 1.2–21.1). Worry was also associated with high absolute risk perception and former smoking. Factors associated with higher risk perception were age>60 years, at-risk life style, worry about breast cancer and depression.ConclusionsThe inverse association between early menopause and worry about breast cancer is in contrast with the known protective effect of early menopause on breast cancer risk and seems to reflect a feeling of aging and disease vulnerability. Our findings indicate that worry about cancer has an affective construct which is independent of breast cancer biology but is engaged in health decision making. Increasing breast cancer risk awareness in subjects high in worry without a plan of emotional coping may therefore be counterproductive because of avoidant attitudes.     

Does perceived risk predict breast cancer screening use? Findings from a prospective cohort study of female relatives from the Ontario site of the Breast Cancer Family Registry

While the relationship between perceived risk and breast cancer screening use has been studied extensively, most studies are cross-sectional. We prospectively examined this relationship among 913 women, aged 25–72 with varying levels of familial breast cancer risk from the Ontario site of the Breast Cancer Family Registry. Associations between perceived lifetime breast cancer risk and subsequent use of mammography, clinical breast examination (CBE) and genetic testing were assessed using logistic regression. Overall, perceived risk did not predict subsequent use of mammography, CBE or genetic testing. Among women at moderate/high familial risk, those reporting a perceived risk greater than 50% were significantly less likely to have a CBE (odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.30–0.91, p = 0.04), and non-significantly less likely to have a mammogram (OR = 0.70, 95% CI: 0.40–1.20, p = 0.70) or genetic test (OR = 0.61, 95% CI: 0.34–1.10, p = 0.09) compared to women reporting a perceived risk of 50%. In contrast, among women at low familial risk, those reporting a perceived risk greater than 50% were non-significantly more likely to have a mammogram (OR = 1.13, 95% CI: 0.59–2.16, p = 0.78), CBE (OR = 1.11, 95% CI: 0.63–1.95, p = 0.74) or genetic test (OR = 1.29, 95% CI: 0.50–3.33, p = 0.35) compared to women reporting a perceived risk of 50%. Perceived risk did not significantly predict screening use overall, however this relationship may be moderated by level of familial risk. Results may inform risk education and management strategies for women with varying levels of familial breast cancer risk.     

Risk factors for estrogen receptor positive ductal carcinoma in situ of the breast in African American women

BackgroundCompared to U.S. white women, African American women are more likely to die from ductal carcinoma in situ (DCIS). Elucidation of risk factors for DCIS in African American women may provide opportunities for risk reduction.MethodsWe used data from three epidemiologic studies in the African American Breast Cancer Epidemiology and Risk Consortium to study risk factors for estrogen receptor (ER) positive DCIS (488 cases; 13,830 controls). Results were compared to associations observed for ER+ invasive breast cancer (n = 2,099).ResultsFirst degree family history of breast cancer was associated with increased risk of ER+ DCIS [odds ratio (OR): 1.69, 95% confidence interval (CI): 1.31, 2.17]. Oral contraceptive use within the past 10 years (vs. never) was also associated with increased risk (OR: 1.43, 95%CI: 1.03, 1.97), as was late age at first birth (≥25 years vs. <20 years) (OR: 1.26, 95%CI: 0.96, 1.67). Risk was reduced in women with older age at menarche (≥15 years vs. <11 years) (OR: 0.62, 95%CI: 0.42, 0.93) and higher body mass index (BMI) in early adulthood (≥25 vs. <20 kg/m² at age 18 or 21) (OR: 0.75, 95%CI: 0.55, 1.01). There was a positive association of recent BMI with risk in postmenopausal women only. In general, associations of risk factors for ER+ DCIS were similar in magnitude and direction to those for invasive ER+ breast cancer.ConclusionsOur findings suggest that most risk factors for invasive ER+ breast cancer are also associated with increased risk of ER+ DCIS among African American women.     

Overdiagnosis and overtreatment associated with breast cancer mammography screening: A simulation study with calibration to population-based data

ObjectivesThe magnitude of overdiagnosis of breast cancer associated with mammography screening remains controversial because of methodological issues. The objective of this study was to quantify overdiagnosis and overtreatment associated with a population-based screening programme, taking into account lead time and uncertainty concerning baseline incidence of breast cancers.Material and methodsA simulation model was developed to replicate incidence and detection rates of breast cancer observed in the Isère Département, France. The parameters of the model were estimated using an approximate Bayesian computation method.ResultsFor women aged 50–74 years during the 2007–2010 period, overdiagnosis of non-progressive breast cancers accounted for 17.0% (95% credibility interval (CI): 2.5%–35.5%) of all in situ cancers diagnosed, 5.5% (95% CI: 0.8%–9.8%) of all invasive cancers diagnosed, and 20.3% (95% CI: 3.0%–38.9%) of in situ and 13.0% (95% CI: 2.2%–23.3%) of invasive screen detected breast cancers. The estimates of overdiagnosis due to competitive causes of death were 1.0% (95% CI: 0.2%–%1.7) and 1.1% (95% CI: 0.6%–1.7%) for all in situ and invasive cancers diagnosed, respectively, and 1.3% (95% CI: 0.2%–2.0%) and 2.6% (95% CI: 1.4%–4.0%) of all in situ and invasive screen detected breast cancers, respectively.Among 1000 screen-detected cancers in 2010, 155 (95% CI: 27–284), 134 (95% CI: 10–242) and 140 (95% CI: 25–254) women underwent breast conserving surgery, lymph node dissection and radiation therapy for overdiagnosed cancers, respectively.ConclusionOur estimates of overdiagnosis should be balanced against the reduction of breast cancer mortality to assess the value of breast cancer screening programme.     

Local control in young women with early-stage breast cancer treated with hypofractionated whole breast irradiation

ObjectiveTo compare local control (LC) in young women with early-stage breast cancer (BC) treated with hypofractionated (HF) whole breast irradiation (WBI) vs conventional fractionation (CF) following breast-conserving surgery (BCS).Materials and MethodsWomen <50 years with pT1-2N0 BC following BCS treated with WBI, CF (50Gy/25 fractions) or HF (42.4Gy/16 fractions) followed by a tumor bed boost (10–16Gy/5–8 fractions) from 2009 to 2013 were identified from an institutional database. Median follow-up was 5.2 years (range 0.3–8.4). Kaplan-Meier analysis was used to estimate 5-year LC. Logistic regression identified factors associated with receipt of CF vs HF WBI.ResultsOf 270 eligible women, 227 (84%) were treated with HF and 43 (16%) with CF WBI. A tumor bed boost of 10 Gy/5 fractions was given in 97% of patients, 53% received adjuvant chemotherapy and 94% (225/239) with estrogen-positive disease received endocrine therapy. Median age was 45 years (range 30–49) in HF and 40 years (range 19–49) in the CF group. The 5-year LC rate was 99.3% (95% CI 97.9–100%, p = 0.495) in the HF and 97.5% (95% CI 92.8–100%) in the CF group. On univariate analysis, age ≤ 40 years or triple negative BC was associated with a decreased likelihood of receiving HF WBI. Only age remained significant on multivariate analysis [OR 2.82 (95% CI 1.45–5.48, p = 0.002)].ConclusionsHF WBI was associated with excellent LC rates in this study cohort, comparable to CF WBI. However, CF WBI was more likely to be recommended to women <40 years.     

Patterns of care for ductal carcinoma in situ of the breast: Queensland's experience over a decade

ObjectivesTo review management of ductal carcinoma in situ (DCIS) of the breast in Queensland, with reference to breast conserving surgery (BCS) and adjuvant radiation therapy (RT). In addition, we examined the incidence of invasive breast cancer recurrence and factors predictive of invasive recurrence.Materials and methodsA retrospective review of the Queensland Oncology Repository identified women with resected DCIS (TisN0) ± adjuvant RT between 2003 and 2012. Time to invasive breast cancer recurrence was analysed using the Kaplan Meier method. Median follow-up was 4.9 years.Results3038 women had surgery. 940 (31%) had mastectomy and 2098 (69%) underwent BCS. Of 2098 women having BCS, 1100 (52%) received BCS alone and 998(48%) received adjuvant RT. The use of RT significantly increased over the decade from 25% to 62% (p=<0.001). Clinicopathological factors associated with RT use on multivariate analysis included age ≤70, higher socioeconomic status, larger tumour size, higher nuclear grade and surgical margins ≤5 mm. Invasive breast cancer recurrence at 5 years was 1.7% [95% CI 1.0–3.0] in RT group versus 2.8% [95% CI 2.1–3.8] in BCS alone group. Factors associated with increased risk of invasive recurrence on multivariate analysis were age <40 and surgical margins ≤2 mm.ConclusionThe use of adjuvant RT in Queensland significantly increased between 2003 and 2012. Selection of patients for RT was based on clinicopathological factors associated with higher recurrence risk. Although longer follow-up is required, the selective use of radiation therapy after BCS is associated with a low rate of invasive breast cancer recurrence at 5 years.     

Effects of tamoxifen and aromatase inhibitors on the risk of acute coronary syndrome in elderly breast cancer patients: An analysis of nationwide data

BackgroundAromatase inhibitors (AIs) are the preferred endocrine treatment for postmenopausal hormonal receptor-positive breast cancer. However, there is controversy on the long-term cardiovascular and cerebrovascular safety of AIs over that of tamoxifen.MethodsWe analyzed the National Health Information Database (NHID) of 281,255 women over a 20-year-old diagnosed with breast cancer between 2009 and 2016. Cardiovascular events (CVEs) were defined as the development of the following, acute coronary syndrome (ACS), ischemic and hemorrhagic stroke, defined by using insurance claim records. The model was constructed by Cox proportional hazard regression and this model was used to analyze the effects of AI and tamoxifen on CVE.ResultsWe included 47,569 women for the final analysis. Patients were classified into ‘No hormonal treatment (n = 18,807), ‘Switch (n = 2097)’, ‘Tamoxifen (n = 7081)’ and ‘AI (n = 19,584)’. There were 2147 CVEs in 2032 patients (4.1%). Univariate analysis showed that women with tamoxifen had significantly lower risk for CVEs compared to no-treatment (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74–0.97) while AI showed no such effect (HR 0.93, 95% CI 0.84–1.02). After adjusting for other risk factors (hypertension, dyslipidemia, family history), the use of tamoxifen was associated with significant protective effect against ACS (HR 0.63, 95% CI 0.47–0.84).ConclusionsOur results, based on the NHID, supports the protective effect of tamoxifen against CVE in Korean breast cancer patients aged 55 and older that is not seen with AIs. Our results can guide the selection of adjuvant hormonal treatment agents for Korean breast cancer patients based on their risk of developing CVE.     

Association between common risk factors and molecular subtypes in breast cancer patients

BackgroundBreast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer.MethodsThis cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis.ResultsThousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15–1.74; p = 0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01–2.25; p = 0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03–2.13; p = 0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83–1.88; p = 0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47–0.97; p = 0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53–1.04; p = 0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93–5.17; p = 0.04) and luminal A (OR 1.87, 95% CI 0.93–3.90, p = 0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06–3.37; p = 0.04 and OR 1.90 95% CI 1.00–3.61; p = 0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43–0.95; p = 0.02 and OR 0.50 95% CI 0.32–0.76; p = 0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands.ConclusionsReproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.     

Obstetric complications at time of delivery amongst breast cancer survivors: A population-based cohort study

PurposeOur aim was to determine whether breast cancer survivors are at increased risk of obstetric and maternal complications at time of delivery.MethodsThe USA ‘National Inpatient Sample’ database was queried for hospitalizations associated with deliveries, between 2015 and 2018. The incidence of maternal and fetal complications was compared between women with, and without, a personal history of breast cancer.ResultsOf the 2,103,216 birth related admissions, 617 (0.03%) of the women were breast cancer survivors, with the proportion increasing over time (from 0.02% in 2015 to 0.04% in 2018). Breast cancer survivors had a higher socioeconomic status (p < 0.001) and were significantly older compared to other mothers (34 vs. 28 years, p < 0.001). Additionally, they were more likely to suffer from preexisting chronic diseases including cardiopulmonary disease and diabetes mellitus, and had a higher incidence of multiple gestation (4.4% vs. 1.6%) [OR 2.7, 95% CI 1.9–4.0, p < 0.001]. The incidence of acute adverse events at time of delivery including fetal distress, preterm labor, cesarean section and maternal infection was higher amongst the breast cancer survivors. On multivariate analysis age, ethnic group, comorbidities, multiple gestations, and a previous breast cancer diagnosis, but not cancer treatment, were associated with an increased risk of an obstetric adverse event.ConclusionBreast cancer survivors have more comorbidities and are at increased risk of acute obstetrical complications at time of delivery. Further studies are required to validate these findings, and evaluate the ability of interventions to improve obstetrical outcomes amongst breast cancer survivors.     

Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients

Background: Insulin-like growth factor 1 (IGF-1) has mitogenic properties for breast cancer cell lines and has been proposed to be an important factor in breast carcinogenesis. We hypothesized that differences in IGF-1 or its binding proteins might increase susceptibility to breast cancer. This case-control study was designed to investigate whether patients with breast cancer have altered levels of either IGF-1 or its intermediary modulatory proteins, the IGF binding proteins (BP). Methods: Serum was collected from 90 patients (63 with breast cancer and 27 with benign breast disease) after an overnight fast and before surgery. IGF-1, BP1, and BP3 levels were determined by immunoradiometric assays. In a subset of 66 patients, Western ligand blots were also performed for a semiquantitative measurement of functioning BP levels. A forward stepwise logistic regression model to adjust for other confounding variables (age, menopausal status, parity, age at menarche, use of oral contraceptives, history of breast biopsy, family history of breast cancer, hormone replacement therapy, and body-mass index) was used in the multivariate analysis. Results: Serum IGF-1 levels were similar in cases and controls. However, levels of BP3 (p<0.001), BP4 (p<0.01), and BP1 (p<0.05) were significantly associated with risk of breast cancer. The level of BP3 was the most significant factor predictive of breast cancer. The odds ratio for breast cancer in women with BP3 levels >2066 ng/ml was 0.18 (95% CI, 0.05–0.55). Correspondingly, women with BP1 levels higher than 39 ng/ml had an odds ratio of 0.21 (95% CI, 0.07–0.68) for breast cancer. When considering only cancer patients (n=63), decreasing levels of BP4 (p<0.01) and increasing levels of BP1 (p<0.02) were significantly associated with progesterone receptor positivity (PR+) in the tumor. The odds ratio of PR+ in patients with BP1 levels higher than 34 ng/ml was 7.49 (95% CI, 1.5–37.4). Better grade of tumor (well and moderately differentiated) was observed in patients with higher levels of BP3 (p<0.03). Conclusions: Distinct differences in BP profiles exist among patients with breast cancer and also among those with high-grade, hormonal receptor-negative tumors. These findings suggest that the bioavailability of IGF-1 as mediated by its binding proteins may participate in both breast carcinogenesis and selection of more aggressive breast carcinomas.