Options For Prevention Of Breast Cancer Research Articles

Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

Study protocol: a cluster randomized controlled trial of web-based decision support tools for increasing BRCA1/2 genetic counseling referral in primary care

BackgroundBRCA1 and BRCA2 mutations confer a substantial breast risk of developing breast cancer to those who carry them. For this reason, the United States Preventative Services Task Force (USPSTF) has recommended that all women be screened in the primary care setting for a family history indicative of a mutation, and women with strong family histories of breast or ovarian cancer be referred to genetic counseling. However, few high-risk women are being routinely screened and fewer are referred to genetic counseling. To address this need we have developed two decision support tools that are integrated into clinical care.MethodThis study is a cluster randomized controlled trial of high-risk patients and their health care providers. Patient-provider dyads will be randomized to receive either standard education that is supplemented with the patient-facing decision aid, RealRisks, and the provider-facing Breast Cancer Risk Navigation Toolbox (BNAV) or standard education alone. We will assess these tools’ effectiveness in promoting genetic counseling uptake and informed and shared decision making about genetic testing.DiscussionIf found to be effective, these tools can help integrate genomic risk assessment into primary care and, ultimately, help expand access to risk-appropriate breast cancer prevention options to a broader population of high-risk women.Trial registrationThis trial is retrospectively registered with ClinicalTrials.gov Identifier: NCT03470402: 20 March 2018.

NRG Oncology/National Surgical Adjuvant Breast and Bowel Project Decision-Making Project-1 Results: Decision Making in Breast Cancer Risk Reduction.

Selective estrogen receptor modulators (SERMs) reduce breast cancer risk. Adoption of SERMs as prevention medication remains low. This is the first study to quantify social, cultural, and psychologic factors driving decision making regarding SERM use in women counseled on breast cancer prevention options. A survey study was conducted with women counseled by a health care provider (HCP) about SERMs. A statistical comparison of responses was performed between those who decided to use and those who decided not to use SERMs. Independent factors associated with the decision were determined using logistic regression. Of 1,023 participants, 726 made a decision: 324 (44.6%) decided to take a SERM and 402 (55.4%) decided not to. The most important factor for deciding on SERM use was the HCP recommendation. Other characteristics associated with the decision included attitudes and perceptions regarding medication intake, breast cancer worry, trust in HCP, family members with blood clots, and others' experiences with SERMs. The odds of SERM intake when HCP recommended were higher for participants with a positive attitude toward taking medications than for those with a negative attitude (Pinteraction = 0.01). This study highlights the importance of social and cultural aspects for SERM decision making, most importantly personal beliefs and experiences. HCPs' recommendations play a statistically significant role in decision making and are more likely to be followed if in line with patients' attitudes. Results indicate the need for developing interventions for HCPs that not only focus on the presentation of medical information but, equally as important, on addressing patients' beliefs and experiences. Cancer Prev Res; 10(11); 625-34. ©2017 AACRSee related editorial by Crew, p. 609.

Abstract ES5-3: ES5-3 Targeting the breast, locally: Old and new approaches

Abstract The oldest local approach to breast cancer prevention is surgery. The largest and most rigorous description of this procedure in a high risk population comes from the Mayo Clinic, where 639 women underwent bilateral mastectomy for prevention between 1960 and 1993. Of these procedures, 90% were subcutaneous mastectomies, i.e. ∼90% of the breast was removed, with preservation of the nipple and areola. The breast cancer incidence in this population, with 13 year follow-up, was 90% of the expected incidence. A subset was tested for BRCA1/2 mutations, and among 26 mutations carriers, no cancers were observed. Subsequent studies have focused on more defined high risk populations, mainly carriers of BRCA1/2 mutations. In one recent meta-analysis, the pooled relative risk (RR) was 0.11; 95% CI, 0.04-0.32. However, all-cause mortality was unaffected by mastectomy. Nipple-sparing mastectomy has emerged as an option for mutation carriers recently, and data are beginning to accumulate that overall satisfaction with reconstruction results, and sexual well-being, are greater with the nipple-sparing procedures. The long-term cancer risk data following nipple-sparing procedures are not yet mature. However, mastectomy carries a large physical and emotional cost, which could be avoided if effective non-surgical prevention options were available. Breast cancer prevention in high risk women and those with carcinoma in situ requires that the breast be exposed to an effective agent; systemic exposure is unnecessary, and its harms lead many eligible women to decline preventive therapy. Local transdermal therapy (LTT) to the breast involves the application of active drugs to the breast skin, resulting in high concentrations in the breast but low systemic exposure. It is non-invasive, self-delivered, and not dependent on hepatic metabolism. Existing data on LTT include two pre-surgical window trials of topical 4-hydroxytamoxifen (an active tamoxifen metabolite) in women with invasive breast cancer, and duct carcinoma in situ (DCIS). These demonstrate that LTT with 4-OHT decreases proliferation of invasive and non-invasive cancer cells to a similar degree as oral tamoxifen, with low systemic levels, and no effect on coagulation proteins. These data are promising regarding the use of LTT with 4-OHT for breast cancer prevention, and for therapy of DCIS, but also suggest that LTT could be developed for any small, lipophilic molecule with good dermal permeation, thus greatly expanding the menu of drugs that could be tested for breast cancer prevention. Another locally targeted approach involves the intraductal delivery of active drugs, using a catheter to cannulate the nipple duct orifice. Preliminary studies using Doxil in rodents and in humans have shown this is feasible, but concerns have been raised regarding carcinogenicity of cytotoxic drugs. More recently, RNA interference therapy, and trastuzumab conjugated to a cytotoxic alpha-emitter 225Ac, have been tried in mouse models of DCIS with some success. A trial of intraductal fulvestrant is on-going. Both transdermal and intraductal local therapy approaches hold promise, but are challenging in distinct ways. Nevertheless, ongoing research suggests that local therapy options for breast cancer prevention can move beyond surgical resection of breast tissue. Citation Format: Khan SA. ES5-3 Targeting the breast, locally: Old and new approaches [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES5-3.

Abstract A52: Racial Differences in Prevention Decision Making among Women at High Risk of Breast Cancer

Abstract Background & Objectives: Prior research has documented significant racial disparities in adherence to breast cancer screening recommendations, use of breast-conserving surgery by early stage breast cancer patients, and breast cancer mortality. Decision making about breast cancer prevention options among high risk women has been less thoroughly studied, and racial differences remain mostly unexplored in this arena. The current study employs semi-structured interviews and inductive analytic methods to explore prevention decision making among African American and White women. Its core objective is to investigate the degree to which decision-making processes and outcomes differ across racial groups, and the specific content of these differences, in order to support interventions and programs to facilitate empowered, preventive decision making. Methods: In-depth, semi-structured interviews were conducted with 20 African American and 30 non-Hispanic White women at elevated risk of breast cancer. Allowing women to speak in their own words, these interviews explore women's perception of their risk status; the sources and content of risk information they have obtained; their understanding and consideration of prevention options; decision-making processes; decision-making networks, psychosocial well-being; and women's use of financial, time, and energy resources in coping with risk and prevention. Interviews ranged in length from 30 to 140 minutes and were professionally transcribed. Transcribed data are analyzed through grounded theory methods, using the NVivo 10 software package for qualitative data. Results: High risk African American women's experiences are distinct from those of their White counterparts in a range of ways, including the following. (1) African American women are much less frequently aware of the existence of prophylactic surgeries and chemoprevention options are clinically recommended for women at their own level of risk. (2) Among women who do know about these prevention options, African American women are less likely to consider or undertake prophylactic surgeries or chemoprevention to lower their breast cancer risk. (3) A much higher proportion of African American women have experienced several different types of cancer among their loved ones. These women tend to perceive of themselves as at risk for cancer in general, and not to perceive a specific high risk for breast or ovarian cancer. (4) African American women experience considerably more financial limitations on their ability to access health care and engage in specific prevention activities. Most have been uninsured for some period, and have had at least one health care decision affected by financial constraints. (5) African American women are considerably more likely to reference faith, spirituality, and religion in discussing their perceived risk of cancer and their attitudes toward prevention behavior. Conclusions & Implications: High risk women's narratives reveal substantial racial differences in perceptions, feelings, and choices related to breast cancer prevention. African American women who are clinically determined to be at high risk for breast and ovarian cancer are less likely than similar White women to understand this specific risk, to know about prevention options that could lower the risk, or to consider using these options even when they do know about them. The processes through which African American women navigate risk and prevention are also more heavily influenced by religious faith and financial constraint than those of White women. These distinctions merit further investigation, and confirmation with larger samples. Ultimately, knowledge of such inter-group differences may contribute to tailored interventions to support empowered and health-protective decision making among women at elevated risk. Citation Format: Tasleem J. Padamsee, Anna Muraveva, Electra D. Paskett. Racial Differences in Prevention Decision Making among Women at High Risk of Breast Cancer. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A52.

Willingness to accept preventive bilateral mastectomy among women in rural and urban communities in South-Western Nigeria

Background: Breast cancer is the commonest cancer in women with highest mortality in developing countries due to late presentation. The decision to remove both breasts through preventive bilateral mastectomy among high risk individuals in developing countries would transcend social, cultural and even spiritual boundaries. Preventive mastectomy if considered among women at high risk, can significantly reduces the life time risk of developing breast cancer. The study compared willingness to accept preventive bilateral mastectomy among women who reside in urban and rural communities in South-West Nigeria. Methods: Both quantitative and qualitative methods were employed. The quantitative study was a cross-sectional comparative survey among 680 women aged 20 years and above selected using a multi-stage sampling technique from two predominantly rural and urban Local Government Areas. Participants were interviewed using semi-structured, interviewer-administered questionnaires. In the qualitative study, focus group discussion sessions were held with the women in both rural and urban areas and analysed using detailed content analysis and results presented with Z-Y tables. Quantitative data were analysed using SPSS software version 16.0. Results: Results showed that One hundred and sixty seven (49.1%) and 132 (38.8%) of women in urban and rural areas respectively were willing to accept preventive bilateral mastectomy as a primary prevention strategy if they are identified to be at high risk. (χ 2 =7.3, P = 0.007). For those who were unwilling to accept preventive bilateral mastectomy as an option for breast cancer prevention, the commonest reasons were cosmetic-related (disfigurement and scars). The determinants of willingness to accept preventive bilateral mastectomy among women in rural areas were: self-perceived risk in urban areas and level of education (P = 0.035). Respondents at high self-perceived risk of breast cancer in rural areas were 1.94 times more likely to accept preventive bilateral mastectomy compared with those at average self-perceived risk (OR 1.94, CI 1.22-3.08). Conclusions: The study concluded that respondents with increased knowledge of breast cancer, high level of educational attainment and high self-perceived risk of breast cancer were more likely to accept preventive bilateral mastectomy as a primary prevention strategy if found to be at high risk for developing breast cancer.

State of the Art in Imaging and Chemoprevention for High-Risk Patients

Recent developments in breast imaging technology and chemoprevention clinical trials have provided promising new options for patients at increased risk of breast cancer. Yet there remains much debate and confusion among providers, patients, and insurers regarding accurate breast cancer risk assessment, appropriate breast cancer screening, and options for breast cancer prevention. We review the most recent literature on these topics in order to provide practicing clinicians with current, practical updates on breast cancer prevention and early detection for women at increased risk of breast cancer.

Metformin- A Promising Agent for Chemoprevention in BRCA1 Carriers

Women who carry germline mutations in the BRCA1 gene (BRCA1 carriers) have the highest individual lifetime risk for breast cancer (BCa) known [1-3], with 50% of carriers developing breast cancer by age 50. BRCA2 carriers also have a higher risk but relatively lower than BRCA1 carriers. Currently available options for both BRCA1 and BRCA2 carriers include high-risk surveillance, risk reducing mastectomy or chemoprevention with the ant-estrogens Tamoxifen (TAM) and Raloxifene. Chemoprevention has been controversial in that BRCA1 carriers tend to make estrogen receptor negative tumors. Selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene reduce the risk of estrogen receptor positive breast cancers. For example, results from the National Surgical Adjuvant Breast and Bowel Project (NSABP1) Tamoxifen chemoprevention study suggested that TAM is not effective in carriers of a BRCA1 mutation [4]. Regardless, there is conflicting evidence on this point and both TAM and Raloxifene are offered to BRCA1 carriers as well as BRCA2 carriers [5]. As a chemoprotective agent in the general population, Raloxifene shows a similar reduction in risk for invasive breast cancer to TAM, but not for in situ cancers, which comprise >20% of newly diagnosed cases; the incidence of noninvasive breast cancer is approximately 40% lower for women on TAM compared with Raloxifene [6,7]. Both TAM and Raloxifene are effective only against estrogen receptor-positive tumors [8], and Raloxifene is typically only prescribed in women who are postmenopausal and have decreased bone density [9]. Both drugs increase risk for serious side effects, including venous thrombosis and pulmonary embolism [10,11]. TAM is also associated with an increased risk for endometrial cancer and stroke [12-14]. Other side effects of both drugs include dyspareunia, cataracts, musculoskeletal complaints including leg cramps, weight gain, hot flashes, vaginal discharge, bone loss in premenopausal women and bladder control problems [15]. More recently, long-term administration of TAM was observed to cause hepatic tumors in rats, induced via a genotoxic mechanism [16]. Compounding the unfavorable side affect profile studies have determined that approximately 5 – 10% of the population carries a homozygous variant of the CYP2D6 gene that imparts low activity to convert TAM from its less active form to its active metabolite [17]. This research led the FDA to require a change in the labeling of Tamoxifen to include this information [18]. Concerns about the risk: benefit ratio have thus limited the use of TAM for prevention. Recent evidence suggests that only approximately 8.4% of BRCA carriers who have not undergone prophylactic mastectomy and are eligible to take Tamoxifen or Raloxifene [19], for risk reduction do so [20]. Certainly, there is an urgent need to identify other agents for breast cancer prevention in this high-risk group. In fact, data from our own Inherited Cancer Registry (ICARE) at Moffitt indicated that of 253 female BRCA1 and BRCA2 mutation carriers, 127 had remaining at risk breast tissue (including 40 with a prior breast cancer diagnosis). Of these women, 18.1% indicated that they had taken either TAM or Raloxifene (including 7/60 (11.7%) of BRCA1 carriers and 16/67 (23.9%) of BRCA2 carriers. Consequently, the poor uptake of existing breast cancer prevention options, which appears to be more marked in those with BRCA1 compared to BRCA2, serves to illustrate the urgent need to identify other agents for breast cancer prevention in this high-risk group.

Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR)

This study reports the gynecologic conditions in postmenopausal women (intact uterus on enrollment) in the National Surgical Adjuvant Breast and Bowel Project (NSABP) study of tamoxifen and raloxifene (STAR)/P-2 trial. This study, with a median follow-up period of 81 months, evaluated the incidence rates/risks of gynecologic conditions among women who were treated with tamoxifen and raloxifene. Compared with women who received tamoxifen therapy, women who received raloxifene therapy had a lower incidence of uterine cancer (relative risk, 0.55)/endometrial hyperplasia (relative risk, 0.19), leiomyomas (relative risk, 0.55), ovarian cysts (relative risk, 0.60), and endometrial polyps (relative risk, 0.30) and had fewer procedures performed. Women receiving tamoxifen therapy had more hot flashes (P < .0001), vaginal discharge (P < .0001), and vaginal bleeding (P < .0001). Our results suggest that tamoxifen has more of an estrogenic effect on the gynecologic reproductive organs. These effects should be considered in counseling women on options for breast cancer prevention.

Abstract 5566: In vitro human skin permeation enhancement of endoxifen by oleic acid

Abstract Background: Oral medication for breast cancer prevention is associated with systemic exposure and resulting adverse effects; there is a need for alternative drug delivery approaches. Transdermal drug delivery is such an option, and 4-Hydroxy-N-desmethytamoxifen (endoxifen, ENX) is an excellent candidate for development for this route. ENX is an active metabolite of tamoxifen with major therapeutic effect related to potent estrogen antagonism and ability to cause proteosomic degradation of ERα. We hypothesize that skin permeation of ENX with oleic acid (OA) will be equivalent or superior to that of estradiol (E2), which is a well-established transdermal agent. Methods: Split-thickness human skin samples (354 ± 25 micron) were prepared from de-identified fresh mastectomy specimens under an IRB approved protocol using a surgical blade and placed in Franz diffusion cells (PermeGear, Inc.). ENX was prepared in 60 % (v/v) ethanol/phosphate buffer (PB) +/- OA (0.1to 1% v/v). E2 was used as a positive control drug, prepared in 60 % ethanol/PB. The receiver fluid was PBS, pH 7.4 with 4% (w/v) polyoxyethylene 20 oleyl ether (Sigma-Aldrich). 100 µL of the drug solution (30 µg + 0.1µCi of 3H-E2 or 3H-ENX) was loaded in the donor chamber. Receiver fluid was stirred at 37° C. A sample of receiver fluid was collected for 3H counting from 4 to 24 hr point with 2 hr interval. Each permeation experiment was performed in duplicate for each treatment condition using the breast skin of one individual. The permeation experiments were repeated three times with the skin from different individuals. Results: Results were expressed as the mean and standard deviation (SD) of the % of the applied dose. Absorption is defined as the amount of drug passing into the receiver fluid. We found that the absorption of E2 was 0.2 ± 0.17% (at 12hr) and 3.16 ± 2.79 % (at 24hr) of the applied dose while the absorption of ENX was 0.07± 0.08 % (at 12hr) and 1.45 ± 1.07 % (at 24hr). In the presence of OA, the permeation of ENX was enhanced by 2 to 12- fold at 12 hr and by 1.2 to 3.8- fold at 24 hr. At the 12 hr point, the absorption of ENX alone is one third of that of E2 alone (p = 0.09) however in the presence of 0.25, 0.5, and 1% (v/v) of OA, the absorption of ENX was by 4.4-fold (p = 0.02), 6.4-fold (p = 0.01), and 3-fold (p = 0.02) higher than E2, respectively. At 24 hr, there was no further significant enhancement in the absorption of ENX by 0.25 and 0.5% of OA compared to that of E2. The addition of 0.1 and 1% OA made the absorption of ENX retarded than that of E2 at 24 hr. Conclusion: The skin permeation of ENX was significantly enhanced in the presence of 0.25-1 % of oleic acid and was superior to that of E2 alone at 12 hr. Our results imply that the topical delivery of endoxifen is a potential option for breast cancer prevention with no or minimal systemic toxicity/side effects. Efficacy remains to be demonstrated, but is highly likely given the data on the parent compound (tamoxifen). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5566. doi:10.1158/1538-7445.AM2011-5566

Tamoxifen and the Factor V Leiden Mutation

Both tamoxifen and the factor V Leiden (FVL) mutations are wellestablished risk factors for thromboembolic events (TE). Tamoxifen has been shown to increase risk by two- to fourfold in both adjuvant and preventive trials (1). The FVL mutation is well-established as a risk factor for TE in the general population, with a three- to sixfold relative risk compared with persons without the mutation (2), and it also confers risk in persons in whom excess estrogen stimulation has occurred, such as in women using hormone replacement therapy or high-dose oral contraceptives and in pregnant women (3). Thus, it came as a surprise that among women who took tamoxifen in two major breast cancer prevention trials, FVL carriers carried no excess risk of thromboembolism, despite the fact that tamoxifen itself was a clear and strong risk factor (4,5). In fact for the International Breast Cancer Intervention Study-I (IBIS-I) prevention trial, among 35 women with an available blood sample who developed a TE (29 of whom received tamoxifen), none were positive for the FVL mutation as compared with eight (5.0%) of the 159 matched control women (6). In addition, none of the women with a TE had the prothrombin G2010A mutation, which is also known to lead to an increased risk of TE (7), as opposed to three women in the control group (1.9%). Similar results were seen in the National Surgical Adjuvant Breast and Bowel Project P1 breast cancer prevention trial (NSABP-P1[BCPT]) (8), in which, again, neither the FVL mutation nor the prothrombin mutation was related to TE risk in tamoxifen users. In this trial, 48 women with a TE were compared with 189 matched controls. Again, tamoxifen was a risk factor for TE, with a relative risk of 1.9 (P = .006). An analysis in breast cancer patients taking tamoxifen that is presented in this issue by Garber et al. (9) found the prevalence of an FVL mutation to be almost fivefold higher in women who had a TE (18.5%) compared with matched control subjects (4.5%) and strongly supports an effect of FVL mutation on risk of TE among tamoxifen users, at least in the adjuvant setting. From these data, it was not possible to determine whether the effects of tamoxifen and the FVL mutation were multiplicative (ie, did not interact) or whether the effect of FVL was stronger or weaker among tamoxifen users than among women who did not take this drug. The incidence of a serious TE during 5 years of treatment with tamoxifen is about 2.4% in adjuvant trials (10), so based on these data, the risk would be more than 10% among FVL carriers and would be clinically relevant. In the prevention setting, the TE risk is substantially less, that is, about 0.6% during 5 years of active tamoxifen treatment in women older than 50 years and even less in younger women (1). Why are the results so apparently different in these two contexts? It could still be due to chance. There were 74 case subjects in the tamoxifen arms of the prevention trials and 124 evaluated case subjects here, and an interaction test gives P = .10. An obvious difference is that the women in this study all had breast cancer, and about 50% had also received chemotherapy, which has been found to be a risk factor for TEs in many other studies (11), but curiously not in the presented article. However, why FVL would predict TE in this setting, but not when tamoxifen is used for prevention, remains a mystery. The issue for breast cancer treatment with tamoxifen is now less important than a few years ago because newer, generally more effective treatments, such as aromatase inhibitors in the postmenopausal setting and luteinizing hormone–releasing hormone agonists in the premenopausal setting, are now available. However, because these newer treatments are not without their own side effects (eg, bone loss and arthralgia), tamoxifen remains a valuable option for some women. In the adjuvant setting, it may be prudent to test for FVL and prothrombin G2010A mutations before starting treatment with tamoxifen. However, the lack of an association between tamoxifen use and TE risk in the prevention trials makes this decision less clear when tamoxifen is used prophylactically. In postmenopausal women, raloxifene is another option for breast cancer prevention, and it does not appear to confer as much risk of TE as tamoxifen (12), but recent evidence also indicates that it is only 75% as effective in preventing breast cancer as tamoxifen (13). Aromatase inhibitors are also being evaluated for breast cancer prevention in high-risk postmenopausal women (14). Continued follow-up and research on the relationship between the FVL mutation and tamoxifen, especially in the prevention setting, will be the only way to clarify these apparently contradictory findings.

Obesity is associated with atypia in breast ductal lavage of women with proliferative breast disease

Background: Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women. Methods: We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors. Results: There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index was also significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia. Conclusions: Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk.

Breast Cancer Risk Assessment and Prevention: A Framework for Shared Decision-Making Consultations

Options for breast cancer prevention, used in combination with screening and surveillance, include lifestyle modifications, chemoprevention with tamoxifen, and prophylactic surgery. Preventive health decisions are often preference driven: patients typically must choose whether to initiate effective treatments that hold the possibility of side effects that can negatively impact quality of life. This situation demands that patients be well informed and have a full understanding of the risks associated with each option. Investigators have developed a comprehensive decision-making framework designed to support breast cancer prevention consultations within a shared decision-making setting. The framework integrates predictive information from current risk models within the context of a woman's general health to appropriately frame breast cancer risk management consultations and outlines the application of available treatments and emerging biomarker information to individual patient decisions. Using an evidence-based approach, specialized risk-benefit projections can be provided in the clinical setting. A more comprehensive individualized risk profile allows for tailored medical management plans and can better prepare patients to make informed decisions. The framework is intended to encourage a shared decision-making approach to prevention consultations, a method for researchers to increase accrual to trials, and to more quickly incorporate new findings into the routine of practice.

Energy balance and breast cancer risk.

We evaluated the hypothesis that a pattern of behavioral exposures indicating positive energy balance [i.e., less exercise/sport activity, high body mass index (BMI), or high energy intake] would be associated with an increased breast cancer risk in the Shanghai Breast Cancer Study, a population-based study of 1,459 incident breast cancer cases and 1,556 age frequency-matched controls. Participants completed in-person interviews that collected information on breast cancer risk factors, usual dietary intake and physical activity in adulthood. Anthropometric indices were measured. Odds ratios and 95% confidence intervals were estimated by logistic regression to describe the individual and joint effects of the exposures on breast cancer risk. Lack of exercise/sport activity, low occupational activity, and high BMI were all individually associated with increased risk of breast cancer [odds ratios (OR) ranged from 1.49 to 1.86]. In general, women with lower exercise/sport activity level and higher BMI, or those with higher energy intake, were at an increased risk compared with women who reported more exercise/sport activities, had lower BMIs, or reported less energy intake. There was a significant multiplicative interaction (P = 0.02) between adult exercise/sport activity and BMI, with inactive women in the upper BMI quartile being at increased risk (OR, 2.16; 95% confidence interval, 1.25-3.74) compared with their active and lean counterparts. This association was stronger in postmenopausal than in premenopausal women, and non-exercising postmenopausal women with higher BMIs were at substantially increased risk (OR, 4.74; 95% confidence interval, 2.05-12.20). Our study suggests that promotion of behavior patterns that optimize energy balance (weight control and increasing physical activity) may be a viable option for breast cancer prevention.

Proceedings of the Fourth International Conference on Recent Advances and Future Directions in Endocrine Manipulation of Breast Cancer: Conference Summary Statement

Proceedings of the Fourth International Conference on Recent Advances and Future Directions in Endocrine Manipulation of Breast Cancer: Conference Summary Statement

Advances in Screening, Diagnosis, and Treatment of Breast Cancer

Advances in Screening, Diagnosis, and Treatment of Breast Cancer

Addressing the support needs of women at high risk for breast cancer: evidence-based care by advanced practice nurses.

To identify support needs of women at high risk for breast cancer and enhance an evidence-based service. Descriptive study. A comprehensive, breast-health service for high-risk women. 97 high-risk women with a 1.66% or greater five-year risk of breast cancer, atypical hyperplasia, lobular carcinoma in situ, or positive genetic screen. A self-assessment questionnaire completed previsit and a satisfaction survey completed postvisit. Women's perceived informational, emotional, and decisional support needs, current self-care practices, and satisfaction with the service provided. Women under age 50 (n = 54) wanted information on breast cancer screening, risk of breast cancer, lifestyle options to lower risk, and hormone replacement therapy; older women (n = 43) wanted information on risk of breast cancer, lifestyle options, breast cancer screening, and chemoprevention. More than 75% of all women wanted information to help them make decisions on breast cancer prevention options, benefits, and risks. The satisfaction survey (N = 61) revealed that most women's needs were met. Support needs were consistent with the literature that focused primarily on younger women seeking genetic counseling. Proactive planning assisted with addressing the needs of these women. A previsit questionnaire facilitates individualized proactive planning before the visit. However, further assessment of self-care practices and emotional needs is required. Interventions should evaluate outcomes, such as accurate risk perception, lifestyle changes, screening follow-through, and decision quality. Advanced practice nurses require specialized skills, including evidence-based risk communication, behavior modification, and decision support.

Breast cancer epidemiology, prevention, and early detection.

Breast cancer remains a worldwide public health concern despite the fact that mortality rates have been declining in some countries as a result of improvements in adjuvant therapy and screening for breast cancer. In the prevention arena, advances in our understanding of the effects of tamoxifen have led to the investigations of newer agents that may provide extended options for breast cancer prevention in high-risk women. For women who are carriers of a mutation in the breast cancer susceptibility genes BRCA1 or BRCA2, prophylactic oophorectomy and bilateral mastectomy have emerged as preventative surgical options that can significantly impact breast cancer risk. In addition, the identification of potentially modifiable risk factors for breast cancer such as dietary folate intake, alcohol consumption, physical activity, and certain anthropometric factors provides opportunities for intervening in breast cancer prevention both among women at average and high risk. The challenge remains in overcoming the limitations of mammography and clinical breast examination by developing and evaluating new technologies for breast cancer screening such as digital mammogram and breast magnetic resonance imaging.