Noncontraceptive hormone use and risk of breast cancer

All British Columbia (Canada) women under 75 years of age who were diagnosed with breast cancer during 1988–89 were asked to complete a postal questionnaire which included detailed information on menopausal estrogen use. Controls were drawn from the Provincial Voters List, matched by five-year age category to the cases. The present analysis consists of 699 cases and 685 controls who were postmenopausal due to natural causes or to a hysterectomy. There was no overall increase in risk of breast cancer associated with ever-use of unopposed estrogen (odds ratio [OR] = 1.0,95 percent confidence interval [CI] = 0.8–1.3). For estrogen use of 10 years or longer, the relative risk [RR] was 1.6 (CI = 1.1–2.5). The risk estimate for current users was somewhat elevated (OR = 1.4, CI = 1.0–2.0). Compared with women who never used hormone preparations, women who had used estrogen plus progestogen had an RR of 1.2 (CI = 0.6–2.2). Our results suggest that ever-use of estrogen, with or without progestogen, does not appreciably increase the risk of breast cancer. However, long-term and recent use of unopposed estrogen may be associated with a moderately increased risk.Drs Yang and Band, and Mr Gallagher are with the British Columbia Cancer Agency, Vancouver, Britsh Columbia, Canada. Authors are also affiliated with the School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA (Drs Yang, Daling, White, and Weiss), and the Fred Hutchinson Cancer Research Center, Seattle, WA, USA (Drs Daling, White, and Weiss). Address correspondence to Mr Gallagher, Division of Epidemiology, Biometry and Occupational Oncology, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC, Canada, V5Z 4E6. This project is funded partially by Health and Welfare Canada, Grant #6610-1834-55 and by Workers Compensation Board of BC.     

Organization-based performance measures of cancer care quality: core measure development for breast cancer in Taiwan

The purpose of the study was to develop organization-based core performance measures (CPMs) for breast cancer patients treated in hospitals that participated in cancer quality improvement programmes in Taiwan. CPMs were developed in three stages that included a preparation, a consensus building stage, and two stages of stakeholder feedback. Three criteria and seven subcriteria were applied in the development process. Indicators listed in a Delphi questionnaire were based on a literature search, indicators developed by relevant institutions and discussion by authors. Each indicator needed to meet inclusion criteria as a final indicator. Evidence-based guidelines, expert opinions from panel group, 27 hospitals and empirical data were all applied to develop and revise the core measures. Fifteen out of 28 indicators were selected and modified after the three stages. There were two pre-treatment indicators for screening and diagnosis, nine treatment-related indicators, and four monitoring-related indicators. Six indicators were supported by evidence level I, and four indicators by level II evidence. The CPMs for breast cancer can be developed systematically and be applied for internal quality improvement and external surveillance. Our experience can be extended to other cancer sites and adapted to link with pay for performance or certification program in cancer care.     

Adjuvant chemotherapy in breast cancer: To use or not to use,the anthracyclines

Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclines in the adjuvant setting for patients with breast cancer. We consulted PubMed, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review.     

First Surgical National Consensus Conference of the Italian Breast Surgeons association (ANISC) on breast cancer management in neoadjuvant setting: Results and summary

RationaleOn October 15th, 2020, the first Surgical National Consensus Conference on neoadjuvant chemotherapy (NACT) was promoted by the Italian Association of Breast Surgeons (ANISC).MethodThe Consensus Conference was entirely held online due to anti-Covid-19 restrictions and after an introductory four lectures held by national and international experts in the field, a total of nine questions were presented and a digital “real-time” voting system was obtained. A consensus was reached if 75% or more of all panelists agreed on a given question.ResultsA total of 202 physicians, from 76 different Italian Breast Centers homogeneously distributed throughout the Italian country, participated to the Conference. Most participants were surgeons (75%). Consensus was reached for seven out of the nine considered topics, including management of margins and lymph nodes at surgery, and there was good correspondence between the 32 “Expert Panelists” and the “Participants” to the Conference. Consensus was not achieved regarding the indications to NACT for high-grade luminal-like breast tumors, and the need to perform an axillary lymph node dissection in case of micrometastases in the sentinel lymph node after NACT.ConclusionsNACT is a topic of major interest among surgeons, and there is need to develop shared guidelines. While a Consensus was obtained for most issues presented at this Conference, controversies still exist regarding indications to NACT in luminal B-like tumors and management of lymph node micrometastases. There is need for clinical studies and analysis of large databases to improve our knowledge on this subject.     

A perfect storm: How tumor biology,genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change

It is well known that there is a significant racial divide in breast cancer incidence and mortality rates. African American women are less likely to be diagnosed with breast cancer than white women but are more likely to die from it. This review explores the factors that may contribute to the racial survival disparity. Consideration is paid to what is known about the role of differences in tumor biology, genomics, cancer screening, and quality of cancer care. It is argued that it is the collision of 2 forces, tumor biology and genomics, with patterns of care that leads to the breast cancer mortality gap. The delays, misuse, and underuse of treatment for African American patients are of increased significance when these patients are presenting with more aggressive forms of breast cancer. In the current climate of health care reform ushered in by the Affordable Care Act, this article also evaluates interventions to close the disparity gap. Prior interventions have been too narrowly focused on the patient rather than addressing the system and improving care across the continuum of breast cancer evaluation and treatment. Lastly, areas of future investigation and policy initiatives aimed at reducing the racial survival disparity in breast cancer are discussed. CA Cancer J Clin 2015;65: 221–238. © 2015 American Cancer Society.     

Type of postmenopausal hormone use and risk of breast cancer: 12-year follow-up from the Nurses' Health Study

We prospectively examined the use of hormone replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 12 years of follow-up (480,665 person-years) among postmenopausal women, 1,050 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk. After adjustment for established risk factors, type of menopause, age at menopause, and current age, the rate ratio (RR) was 0.91, 95 percent confidence interval (CI) = 0.78–1.07. the risk of breast cancer was elevated significantly among current users (RR = 1.33, CI = 1.12–1.57); after adjusting for age, we observed no evidence of increasing risk with increasing duration of use among current users (P trend = 0.41), or among past users (P trend = 0.46). Women currently using unopposed estrogen (RR = 1.42, CI = 1.19–1.70), estrogen and progesterone (RR = 1.54, CI = 0.99–2.39), or progesterone alone (RR = 2.52, CI = 0.66–9.63), were all at increased risk of breast cancer compared with never users. These data suggest that long-term past use of estrogen replacement therapy is not related to risk, that current estrogen use increases risk of breast cancer to a modest degree, and that the addition of progesterone does not remove the increased risk observed with current use of unopposed estrogen.The authors are with the Nurses' Health Study, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA; and Harvard Medical School, Boston, MA, USA. Address correspondence to Dr Colditz, Channing Laboratory, 180 Longwood Ave., Boston, MA 02115-5899, USA. Supported by research grant CA40356 from the National Cancer Institute, NIH, Department of Health and Human Services. Dr Colditz is supported by an American Cancer Society Faculty Research Award FRA-398.     

Evaluating the performance of models for predicting the BRCA germline mutations in Han Chinese familial breast cancer patients

Purpose Established models (Penn, Myraid and BRCApro) are useful of estimating the probability that a person has a BRCA mutation. But the value of these models in Chinese population is unclear. The aim of the study is to evaluate the performance of three models on the assisting in pre-test genetic risk counseling. Methods Three risk assessment models, Penn II, Myriad and BRCApro, were applied to 212 familial breast cancer patients who had undergone BRCA1/2 mutation analysis. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operator characteristic (ROC) curve were calculated for each model. Results Myriad showed a better ROC curve than BRCApro either for BRCA1 or BRCA1/2 combination mutation prediction, but BRCApro had a higher positive likelihood ratio when using 10% as the probability threshold. The performance of three models improved when they were evaluated in 66 patients from high risk families, presenting increased ROC and positive likelihood ratio. Especially that of BRCApro for BRCA2, the ROC was increased to 0.716 and its positive likelihood was 5.6. Conclusion Three models had the similar impact on the pre-test probability of BRCA mutation. But at a 10% cutoff point, BRCApro had the best BRCA mutation carrier prediction value. The performance of BRCApro for BRCA2 mutation prediction was improved when it was restricted in patients from high risk families. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Nan-Yan Rao and Zhen Hu are contributed equally to this work.     

Facilitating reproductive choices: the impact of health services on the experiences of young women with breast cancer

Objective: Chemotherapy and hormone treatments carry significant implications on the fertility of young women with breast cancer. Increasingly, nulliparous women experience fertility dilemmas due to rising survival rates and pregnancy delay. This qualitative study investigated women's responses to being told that treatments affected their fertility and how their interactions with health services impacted on their experiences. Methods: Twenty‐four women under 40 years participated in three focus groups using a flexible interview structure. Data were analysed using content analysis and participants subsequently member checked the themes generated. Results: The priority for most women was survival, although women without children were more willing to take risks. Many women felt that pregnancy after breast cancer and methods of egg harvesting carried a significant risk to survival and fears appeared to be increased by conflicting advice from health professionals. Overall, the women felt the cancer, its treatment options and the health service itself had each robbed them of choice. Hence, with hindsight, many said they would have welcomed an open and honest discussion with a fertility expert to maximise their options. Conclusions: Young women with breast cancer face complex decisions regarding their fertility and treatment options. Survival remains the priority for the majority of women. Although there is a paucity of evidence concerning many fertility issues, it is essential that available options and any potential risks are discussed in a coherent, objective fashion. Early referral to specialist fertility services that provide clear, cohesive advice can aid informed decision making. Copyright © 2010 John Wiley & Sons, Ltd.     

Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer

PURPOSE: A 1998 meta-analysis of postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC) found that PORT did not improve outcomes. Yet practice guidelines differ in their recommendations with regard to PORT use. We examine temporal trends in PORT use before and after the 1998 meta-analysis. METHODS AND MATERIALS: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we identified 22,953 patients with Stage I, II, or IIIA NSCLC who had resection between 1992 and 2002 in the United States and characterized each patient according to nodal status (N0, N1, or N2 disease). We measured use of PORT by calendar year. We examined the association between clinical and demographic characteristics and receipt of PORT using logistic regression. RESULTS: For N0, N1, and N2 NSCLC, PORT use has declined. The proportion of patients with N0 disease receiving PORT declined from 8% in 1992 to 4% in 2002. For patients with N1 disease, PORT use declined from 51% in 1992 to 19% in 2002; and for patients with N2 disease, PORT use declined from 65% in 1992 to 37% in 2002. CONCLUSION: In the context of uncertainty about what constitutes optimal adjuvant treatment for resected NSCLC, PORT use has substantially declined.     

Analysis of referrals to a multi-disciplinary breast cancer genetics clinic: practical and economic considerations

Analysis of activity was undertaken in an established regional clinic providing risk assessment, counselling, screening and management for women with a family history of breast or ovarian cancer. The objectives were to determine: (1) how closely the route and pattern of referrals matched official guidelines (2) whether the previously recorded socio-economic imbalance among clinic clientele persisted and (3) the economic and practical consequences of committing resources to verification and extension of reported family histories. The findings were: (1) after some years of operation, the proportion of referrals direct from primary care had increased from less than 50% to over 75%, with a concomitant slight decrease in overall referral rate; (2) the socio-economic distribution of patients referred had become less selective and (3) extension and verification of reported family histories led to a redistributuion of risk categories, increasing the proportion of referrals judged to be in the “low risk” category, from 25% (based on referral letter alone) to 41% (at the end of the process). The costs associated with this approach are offset by the savings generated and it allows specialised counselling and screening services to be targeted more efficiently.     

Challenges to the early diagnosis and treatment of breast cancer in developing countries

This critical review of the literature assembles and compares available data on breast cancer clinical stage, time intervals to care, and access barriers in different countries. It provides evidence that while more than 70% of breast cancer patients in most high-income countries are diagnosed in stages I and II, only 20%-50% patients in the majority of low- and middle-income countries are diagnosed in these earlier stages. Most studies in the developed world show an association between an advanced clinical stage of breast cancer and delays greater than three months between symptom discovery and treatment start. The evidence assembled in this review shows that the median of this interval is 30-48 d in high-income countries but 3-8 mo in low- and middle-income countries. The longest delays occur between the first medical consultation and the beginning of treatment, known as the provider interval. The little available evidence suggests that access barriers and quality deficiencies in cancer care are determinants of provider delay in low- and middle-income countries. Research on specific access barriers and deficiencies in quality of care for the early diagnosis and treatment of breast cancer is practically non-existent in these countries, where it is the most needed for the design of cost-effective public policies that strengthen health systems to tackle this expensive and deadly disease.     

利用 ROC 曲线评价 CEA、CA153在 HER -2阳性乳腺癌术后随访中的价值

目的：用ROC曲线评价CEA及CA153监测HER-2阳性乳腺癌患者术后复发转移的价值,并确立诊断HER-2阳性乳腺癌患者术后复发转移的最佳临界值。方法收集127例HER-2阳性乳腺癌患者CEA及CA153数值,将其分为复发转移及未复发转移两组。绘制ROC曲线,找到最佳临界值,同时比较最佳临界值与常规诊断值诊断复发转移的优劣。结果复发转移组较未复发转移组CEA及CA153水平显著偏高（P＜0．0001）,CEA、CA153诊断复发转移ROC曲线下面积分别为0．752、0．820,对应的最佳临界值分别为3．5 ng/mL、17．89 U/mL。 CEA和CA153最佳临界值敏感性分别为46．15％、65．38％,CEA和CA153最佳临界值特异性分别为97．33％、89．33％。结论 CEA、CA153在HER-2阳性乳腺癌患者术后判断复发转移中具有中等价值,诊断术后复发转移的最佳临界值分别为3．5 ng/mL、17．89 U/mL。     

Parental age at delivery and incidence of breast cancer: a prospective cohort study

Background Studies on parental age at delivery in relation to breast cancer risk have had mixed results, but prospective data are limited. No study has explored the associations with subtypes of breast cancer defined by hormonal receptor status. Methods 109,773 women in the Nurses’ Health Study were followed from 1976 to 2002. We used Cox proportional hazards model to examine the association between parental age at delivery and daughters’ risk of breast cancer. Results 6,827 incident cases of invasive breast cancer occurred in this cohort during 2,581,098 person-years. Adjusting for other early life exposures and family history of breast cancer, the hazard ratio for breast cancer in women born to mothers aged 21–25, 26–30, 31–35, and ≥36 years was, respectively, 1.08 (95% CI: 0.99–1.18), 1.12 (95% CI: 1.03–1.23), 1.17 (95% CI: 1.06–1.29), and 1.12 (95% CI: 1.01–1.25), compared to women born to mothers aged ≤20 years (P for trend = 0.008). Similarly, advanced paternal age was associated with increased incidence of breast cancer (P for trend = 0.03), but the association disappeared when conditioning on maternal age. The positive association between maternal age and incidence of breast cancer was stronger for estrogen receptor-positive and progesterone receptor-positive tumors (P for trend = 0.003) than for tumors with both receptors negative (P for trend = 0.78), and was more consistent among postmenopausal women, women without a family history and women who were first born. Conclusion Our findings support a modest positive association between maternal age and daughter’s risk of breast cancer, possibly mediated by hormonal factors.     

Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experience

Background

Metabolic Syndrome (MS) has been correlated to breast carcinogenesis. MS is common in the general population (34%) and increases with age and body mass index. Although the link between obesity, MS and hormone related cancer incidence is now widely recognized, the molecular mechanisms at the basis of such increase are still poorly characterized. A crucial role is supposed to be played by the altered insulin signalling, occurring in obese patients, which fuels cancer cell growth, proliferation and survival. Therefore we focused specifically on insulin resistance to investigate clinically the potential role of insulin in breast carcinogenesis.

Methods

975 patients were enrolled and the association between MS, insulin resistance, and breast cancer was evaluated. Women were stratified by age and menopausal status. Insulin resistance was measured through the Homeostasis Model Assessment score (HOMA-IR). The cut off value to define insulin resistance was HOMA-IR ≥ 2.50.

Results

Higher prevalence of MS (35%) was found among postmenopausal women with breast cancer compared to postmenopausal healthy women (19%) [OR 2.16]. A broad range of BMI spanning 19–48 Kg/m² was calculated. Both cases and controls were characterized by BMI ≥ 25 Kg/m² (58% of cases compared to 61% of controls). Waist circumference >88 cm was measured in 53% of cases - OR 1.58- (95% CI 0.8-2.8) and in 46% of controls. Hyperinsulinemia was detected in 7% of cases – OR 2.14 (95% CI 1.78-2.99) and only in 3% of controls. HOMA-IR score was elevated in 49% of cases compared to 34% of controls [OR 1.86], suggesting that insulin resistance can nearly double the risk of breast cancer development. Interestingly 61% of women operated for breast cancer (cases) with HOMA-IR ≥ 2.5 presented subclinical insulin resistance with fasting plasma glucose levels and fasting plasma insulin levels in the normal range. Both android fat distribution and insulin resistance correlated to MS in the subgroup of postmenopausal women affected by breast cancer.

Conclusions

Our results further support the hypothesis that MS, in particular insulin resistance and abdominal fat, can be considered as risk factors for developing breast cancer after menopause. We suggest that HOMA-IR, rather than fasting plasma glucose and fasting plasma insulin levels alone, could be a valuable tool to identify patients with subclinical insulin resistance, which could be relevant for primary prevention and for high risk patient screening.     

Cervical cancer metastatic to the breast: a case report and review of the literature

Metastasis to the breast from primary cervical cancer is rare. We describe one such patient, who developed breast metastasis 6 months after diagnosis. She was free of pelvic disease at the time of metastases but had evidence of lung involvement. She died of progressive disease 2 months later. Data on 23 patients collected from the literature via Medline are reviewed.     

Cosmetic reconstruction after resection of breast cancer: use of the ELD-MC flap and EVRAM flap

Breast reconstruction following the resection of breast cancer with inadequate residual chest-wall tissue may be performed with an implant or a myocutaneous flap, such as the latissimus dorsi or a rectus abdominis. Among a variety of operative procedures, each method has advantages and disadvantages. The insertion of a silicone-bag prosthesis is the easiest method, but the prosthetic implant sometimes has complications, such as unfavorable capsular contracture formation around the implant, rupture, infection, or exposure. We therefore use an extended latissimus dorsi myocutaneous (ELD-MC) flap with some amount of surrounding subcutaneous fat from the lumbar area, and avoid the use of any implant with an MC flap. Also, for the reconstruction and correction of infraclavicular and axillary depression, we use the extended vertical rectus abdominis myocutaneous (EVRAM) flap. This method uses the skin and fat on both sides of the umbilicus as a lenticular flap vascularized by only one of the rectus abdominis muscles. The patients are satisfied with the outcome because symmetry and good breast volume can be obtained. There have been no functional or anatomical defects of the donor area. No abdominal hernia after an EVRAM flap has resulted to date. Both the ELD-MC and EVRAM flaps can be successfully used for cosmetic breast reconstruction after the resection of breast cancer.     

Canadian initiatives for locally advanced breast cancer research and treatment: inaugural meeting of the Canadian Consortium for LABC

The inaugural Canadian Consortium for LABC (locally advanced breast cancer) conference was held at Langdon Hall, Cambridge, Ontario, April 11–12, 2010. The meeting focused on current and future directions in labc treatment and research, the specific benefits of labc as a model for clinical and translational research, strategies for increased national and international collaboration, and ongoing clinical trials. Exciting Canadian initiatives in labc research are underway, focusing on identifying molecular signatures that will allow for the development of new tailored therapies. The challenge of identifying patient subgroups for accrual is being addressed through strategies to foster and improve national collaboration. This meeting report includes highlights from each presentation at the conference.     

Characterization of inflammatory changes in the breast cancer associated adipose tissue and comparison to the unaffected contralateral breast

BackgroundAdipose tissue has emerged as an important window into cancer pathophysiology, revealing potential targets for novel therapeutic interventions. The goal of this study was to compare the breast adipose tissue (BrAT) immune milieu surrounding breast carcinoma and contralateral unaffected breast tissue obtained from the same patient.Materials and methodsPatients undergoing bilateral mastectomy for unilateral breast cancer were enrolled for bilateral BrAT collection at the time of operation. After BrAT was processed, adipocyte and stromal vascular fraction (SVF) gene expression was quantified by PCR. SVF cells were also processed for flow cytometric immune cell characterization.ResultsTwelve patients underwent bilateral mastectomy for unilateral ductal carcinoma. BrAT adipocyte CXCL2 gene expression trended higher in the tumor-affected breast as compared to the unaffected breast. Macrophage MCP-1 and PPARγ gene expression also tended to be higher in the tumor-affected breasts. T cell gene expression of FOXP3 (p = 0.0370) were significantly greater in tumor-affected breasts than unaffected breasts. Affected BrAT contained higher numbers of Th2 CD4⁺ cells (p = 0.0165) and eosinophils (p = 0.0095) while trending towards increased macrophage and lower Th1 CD4⁺ cells infiltration than tumor-affected BrAT.ConclusionThis preliminary study aimed to identify the immunologic environment present within BrAT and is the first to directly compare this in individual patients’ tumor-associated and unaffected BrAT. These findings suggest that cancer-affected BrAT had increased levels of T cell specific FOXP3 and higher levels of anti-inflammatory/regulatory cells compared to the contralateral BrAT.