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.     

Type and Duration of Exogenous Hormone Use Affects Breast Cancer Histology

Background It is unclear whether hormone replacement therapy (HRT), in addition to increasing risk for breast cancer, affects the type of breast cancer diagnosed. We conducted this investigation to assess whether the type of hormone used (none, estrogen, progesterone, or combined) and duration of use influences subsequent breast cancer histology. Methods We performed a retrospective cohort analysis among women listed as incident cases of breast malignancy in the Kaiser Permanente Northern California Cancer Registry during 2003 (n = 2830). Type and duration of hormone used (none, estrogen, progesterone, or combined) before breast cancer diagnosis was obtained from electronic pharmacy records. The association between type and duration of hormone use with characteristics of subsequent breast cancers was examined. Results Among women aged >50 years (n = 1701), any use of estrogen, progesterone, or combination therapy was not associated with an increased risk of estrogen receptor (ER)-positive disease. However, >6 months’ use of combined HRT increased the odds of ER-positive tumors (odds ratio, 1.65; 95% confidence interval, 1.07–2.5; P = .02). Estrogen HRT patients were more likely than nonusers to present with low-grade (P = .05), and early-stage tumors (P = .03). This trend was not seen in combined HRT users. Conclusions Short-duration HRT did not increase the likelihood of ER-positive breast cancer. However, prolonged duration of combined HRT, but not estrogen or progesterone alone, resulted in a marked increase in ER-positive disease. Our findings suggest that the effect of combined HRT on breast cancer incidence or progression is not immediate and that long-term use is more likely to affect breast cancer histology.     

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.     

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.     

Prolactin and Breast Cancer Etiology: An Epidemiologic Perspective

A number of epidemiologic studies of prolactin and breast cancer etiology have recently become available. Retrospective case-control studies have suggested a modest positive or null relationship between circulating prolactin concentrations and risk of breast cancer. However these studies are limited by small sample sizes and the collection of blood after case diagnosis. Several large prospective studies, in which blood was collected prior to diagnosis, have observed modest positive associations between prolactin and risk. In a pooled analysis of ~80% of the world’s prospective data, the relative risk (RR) comparing women in the top vs bottom quartile of prolactin levels was 1.3 (95% confidence interval (CI): 1.1, 1.6, p-trend = 0.002). The results were similar for premenopausal and postmenopausal women. Most notably, high prolactin levels were associated with a 60% increased risk of estrogen receptor (ER) positive tumors, but not with ER negative tumors. Limited genetic data suggest a role of polymorphisms in the prolactin and prolactin receptor genes in risk of breast cancer. Studies of survival have suggested that high pretreatment prolactin levels were associated with treatment failure, earlier recurrence, and worse overall survival. Parity and certain medications are the only confirmed factors associated with prolactin levels in women. Overall, epidemiologic data suggest that prolactin is involved in breast cancer etiology. Further research to better elucidate these associations and their underlying mechanisms is warranted.     

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.     

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.     

Clinical and genetic risk factors for aromatase inhibitor-associated arthralgia in breast cancer survivors

BackgroundArthralgia is a common and debilitating toxicity of aromatase inhibitors (AI) that leads to premature drug discontinuation. We sought to evaluate the clinical and genetic risk factors associated with AI-associated arthralgia (AIAA).MethodsWe performed a cross-sectional study among postmenopausal women with stage 0-III breast cancer who were prescribed a third-generation AI for adjuvant therapy. The primary outcome was patient-reported AIAA occurrence. We extracted and assayed germline DNA for single nucleotide polymorphisms (SNPs) of genes implicated in estrogen and inflammation pathways. Multivariable logistic regression models examined the association between demographic, clinical, and genetic factors and AIAA. Analyses were restricted to White participants.ResultsAmong 1049 White participants, 543 (52%) reported AIAA. In multivariable analyses, women who had a college education [Adjusted Odds Ratio (AOR) 1.49, 95% Confidence Interval (CI) 1.00–2.20], had a more recent transition into menopause (<10 years) (5–10 years AOR 1.55, 95% CI 1.09–2.22; <5 years AOR 1.78, 95% CI 1.18–2.67), were within one year of starting AIs (AOR 1.61, 95% CI 1.08–2.40), and those who received chemotherapy (AOR 1.38, 95% CI 1.02–1.88) were significantly more likely to report AIAA. Additionally, SNP rs11648233 (HSD17B2) was significantly associated with higher odds of AIAA (AOR 2.21, 95% CI 1.55–3.16).ConclusionsTime since menopause and start of AIs, prior chemotherapy, and SNP rs11648233 within the HSD17B2 gene in the estrogen pathway were significantly associated with patient-reported AIAA. These findings suggest that clinical and genetic factors involved in estrogen withdrawal increase the risk of AIAA in postmenopausal breast cancer survivors.     

Scalp cooling successfully prevents alopecia in breast cancer patients undergoing anthracycline/taxane-based chemotherapy

IntroductionChemotherapy for breast cancer induces alopecia, representing a major source of patient distress. This study assesses whether a scalp-cooling device is effective in reducing chemotherapy-induced alopecia, and assesses adverse treatment effects.Materials and MethodsA prospective observational study including women with breast cancer undergoing chemotherapy and scalp cooling using a Paxman device. The primary efficacy end points were: successful hair preservation (no hair loss; <30% hair loss not requiring a wig; or <50% hair loss not requiring a wig) at the completion of chemotherapy. Secondary end points included adverse effects such as headache, pain, nausea or dizziness.ResultsThe study enrolled 131 participants. Mean patient age was 49.8 years; 74% received anthracycline/taxane-based chemotherapy and 26% received taxane-monotherapy based chemotherapy. Hair preservation was successful in 102 women who underwent scalp cooling (71.0%; 95% CI = 63–79%). Only adverse events related to device use were collected, representing 7% (95% CI = 3–11%) of cases.ConclusionsScalp cooling is effective in preventing hair loss among breast cancer patients undergoing standard chemotherapy treatment, and has minimal adverse effects.     

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

BackgroundRecent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer.MethodsA single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status.Results608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p = 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR = 0.31, 95% CI 0.11–0.78, p = 0.01), DFS (HR = 0.40, 95% CI 0.20–0.82, p = 0.01) and DDFS (HR = 0.26, 95% CI 0.11–0.63, P = 0.002) compared to women with HER2-0. For women with low genomic risk (RS ≤ 25), long-term prognosis was unrelated to HER2 expression.ConclusionThe prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.     

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.     

Estrogen Replacement Therapy and Breast Cancer: Analysis of Age of Onset and Tumor Characteristics

Background: The use of exogenous estrogen has been scrutinized as a risk factor for breast cancer formation. This prospective study addresses the relationship between the use of estrogen replacement therapy and the age of onset of breast cancer. In addition, an analysis of differences in pathological features of breast cancer between estrogen users and non-estrogen-users was evaluated.Methods: A total of 425 women (age, 50 years) were evaluated during a 4-year period (1994–1997). Data, including the age at diagnosis, method of detection, family history, use of estrogen therapy, and tumor ploidy, S-phase fraction, histological category, estrogen receptor positivity, and grade, were prospectively collected. Data from a control group of 657 women without a diagnosis of breast cancer were obtained from the Evanston Northwestern division of the Womens Health Initiative. Significant associations between the use of estrogen and pathological parameters were determined using the ² test and t-test (P < .05).Results: At the time of breast cancer diagnosis, 140 patients were currently receiving estrogen and 202 patients had no history of estrogen use. Eighty-three patients were excluded from analysis (76 patients had a history of previous but not current use of estrogen therapy, four women used only progesterone, and three patients provided incomplete information). There was no difference between patients with breast cancer using estrogen at the time of diagnosis and those with no history of estrogen use with respect to tumor size, age of menopause, family history, mammographic sensitivity, axillary lymph node status, and histological features. Women using estrogen at the time of diagnosis were younger at the time of breast cancer diagnosis, by an average of 5.1 years (61.3 years vs. 66.4 years, P < .001). Women without a history of breast cancer who were receiving estrogen therapy were an average of 2.4 years younger (63.3 years vs. 65.7 years, P < .001) than women without a history of breast cancer who were not receiving estrogen therapy. Patients with breast cancer receiving estrogen also tended to have more grade II tumors (45.9% vs. 36.5%, P = .045) and fewer grade III tumors (25.6% vs. 37.0%, P =.015), compared with women not receiving estrogen therapy at the time of their diagnoses. Estrogen receptor positivity was noted to be more frequent for estrogen users presenting with lobular carcinoma (85% vs. 76%, P =.042) and less frequent for estrogen users presenting with ductal carcinoma (72% vs. 85%, P = .003).Conclusions: A significantly earlier age of diagnosis for women receiving estrogen therapy suggests that exogenous estrogen may accelerate the pathogenesis of postmenopausal breast cancer. Estrogen therapy may also play a role in altering the grade and estrogen receptor positivity for certain histological types of breast cancer.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Digeo, California, March 26–29, 1998.     

Family history of breast cancer,mammographic breast density and breast cancer risk: Findings from a cohort study of Korean women

BackgroundThis study investigated whether the association between family history of breast cancer in first-degree relatives and breast cancer risk varies by breast density.MethodsWomen aged 40 years and older who underwent screening between 2009 and 2010 were followed up until 2020. Family history was assessed using a self-reported questionnaire. Using Breast Imaging Reporting and Data System (BI-RADS), breast density was categorized into dense breast (heterogeneously or extremely dense) and non-dense breast (almost entirely fatty or scattered areas of fibro-glandular). Cox regression model was used to assess the association between family history and breast cancer risk.ResultsOf the 4,835,507 women, 79,153 (1.6%) reported having a family history of breast cancer and 77,238 women developed breast cancer. Family history led to an increase in the 5-year cumulative incidence in women with dense- and non-dense breasts. Results from the regression model with and without adjustment for breast density yielded similar HRs in all age groups, suggesting that breast density did not modify the association between family history and breast cancer. After adjusting for breast density and other factors, family history of breast cancer was associated with an increased risk of breast cancer in all three age groups (age 40–49 years: aHR 1.96, 95% confidence interval [CI] 1.85–2.08; age 50–64 years: aHR 1.70, 95% CI 1.58–1.82, and age ≥65 years: aHR 1.95, 95% CI 1.78–2.14).ConclusionFamily history of breast cancer and breast density are independently associated with breast cancer. Both factors should be carefully considered in future risk prediction models of breast cancer.     

Radiotherapy concurrent versus sequential with endocrine therapy in breast cancer: A meta-analysis

IntroductionThis study compared treatment outcomes of radiotherapy concurrent with endocrine therapy and radiotherapy sequential with endocrine therapy in breast cancer.Materials and methodsEligible studies of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were retrieved through extensive searches of the PubMed, Medline, Embase, Cochrane library, FEBM, FMJS, Web of science, Wiley, CBM, CNKI, Wang fang, Cqvip databases from 2000 to 2014. Original English and Chinese publications of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were included. The primary endpoint was radiation-induced toxicity including upper than grade 2 skin related toxicity, radiation pneumonia and pulmonary fibrosis; the second endpoint was survival date, including local recurrence, distant metastasis, 5-year OS, 10-year OS.ResultsEleven eligible trials were identified, six in English and five in Chinese. Totally, there were 1291 women in concurrent groups, and 1179 in sequential groups. Statistical analysis showed that there was no statistical difference between concurrent and sequential groups in skin related toxicity (RR 1.20, 95% CI 0.92–1.56, P = 0.17), radiation pneumonia (RR 1.11, 95% CI 0.46–2.70, P = 0.81) and pulmonary fibrosis (RR 1.35, 95% CI 0.75–2.41, P = 0.32). Meanwhile, no statistical difference was found in survival data, (RR 0.97, 95% CI 0.79–1.28, P = 0.26), (RR 0.86, 95% CI 0.66–1.12, P = 0.27) in local recurrence and distant metastasis respectively, (RR 1.01, 95% CI 0.96–1.06, P = 0.65), (RR 0.98, 95% CI 0.93–1.02, P = 0.32) in 5-year and 10-year overall survival respectively. Stratification analysis was proceeded, grouped by tamoxifen and AI in different treatment timing, however, no statistical difference was found in radiation-induced toxicity and survival outcomes.ConclusionRadiotherapy concurrent with endocrine therapy didn't increase or decrease neither the incidence of radiation-induced toxicity nor the survival rate compared with that of sequential group; Endocrine therapy drugs didn't influence outcomes in different treatment timing.     

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.     

Breast cancer after hormone replacement therapy--does prognosis differ in perimenopausal and postmenopausal women?

Hormone replacement therapy (HRT) has been associated with higher incidence of breast cancer in postmenopausal women, but it is unclear if breast cancers developing after HRT use have different prognosis. 1053 women with hormone receptor positive non-metastasized breast cancer were analyzed in a retrospective trial, stratifying by HRT use before diagnosis. Postmenopausal HRT users had significantly more early tumor stages (p < 0.001). HRT in postmenopausal patients was associated with longer time to progression (TTP) (HR 0.81, 95%CI 0.55–1.19, p = 0.28) and overall survival (OS) (HR 0.68, 95%CI 0.45–1.02, p = 0.059). Perimenopausal HRT users showed shorter TTP and OS (HR 1.99, 95%CI 0.57–6.91, p = 0.28 and HR 4.59, 95%CI 0.91–23.25, p = 0.06 respectively). Higher BMI was significantly associated with poorer prognosis in perimenopausal women only (TTP: HR = 1.16; OS: HR = 1.31). In this retrospective analysis postmenopausal HRT users seemed to have a better breast cancer prognosis. For perimenopausal HRT users however, a trend towards worse prognosis was found.     

Importance of patient reported outcome measures versus clinical outcomes for breast cancer patients evaluation on quality of care

IntroductionGiven increasing numbers of breast cancer survivors, there is an increased focus on quality of life and quality of care. This study aims to investigate whether clinical or patient reported outcomes are most important for perceived quality of care by breast cancer patients.MethodsOverall, 606 patients aged 18 years or older, who underwent breast cancer surgery 9–18 months ago in five hospitals in the Netherlands, were invited to complete an internet-based questionnaire. Patients were asked to judge a random selection of 24 patient profiles and choose which of 2 presented patients had received the best quality of care, using conjoint analysis. The individual relative importance (RI) for each outcome was estimated using Hierarchical Bayes Estimation, and averaged over all patients to assess which outcomes were most important.ResultsComplete data were available for 350 patients (58%). Avoiding severe breast symptoms was most important for good quality of care according to patients (RI 23.22 [95% Confidence Interval (95% CI) 22.32–24.12]), followed by a 2 year longer disease free survival (18.30 [17.38–19.22]). However, the importance differed by age: younger patients (<50 years) assigned higher importance to longer disease free survival (21.99 [19.52–24.46]) than older patients (65 + years) (15.03 [13.88–16.18]).ConclusionAvoiding severe breast symptoms rather than 2 year longer disease free survival is considered most important in our population of breast cancer patients for evaluation of quality of care. These data should thus be included in both information provision prior to treatment choices and post treatment quality of care evaluation.     

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.     

Effects of physical exercise on cognitive function of breast cancer survivors receiving chemotherapy: A systematic review of randomized controlled trials

BackgroundCognitive impairment has a great negative impact on quality of life for breast cancer survivors. Emerging evidence suggested that physical exercise can improve cognitive function in order adults with Alzheimer's disease. However, less is known about the effects of physical exercise on cognitive function for breast cancer survivors. The purpose of this meta-analysis was to evaluate the effect of physical exercise on cognitive function in breast cancer survivors.MethodsEMBASE, the Cochrane Library, Web of Science and PubMed were searched from the establishment of the databases to June 2021. Randomized controlled trials were included. All analysis were conducted using the Revman 5.3.Results12 studies (936 participants) indicated that exercise improved self-reported cognitive function (MD 10.12, 95% CI [5.49,14.76], p < 0.0001), cognitive fatigue (MD -5.41, 95% CI [-10.31,-0.51], p = 0.03) and executive function (MD -13.63, 95% CI [-21.86,-5.39], p = 0.0001).ConclusionPhysical exercise can improve cognitive function for breast cancer survivors, particularly in self-reported cognitive function, and executive function. Future studies need to explore the effect of exercise on cognitive function from the frequency and duration of exercise.     

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.