Three-year survival of breast cancer patients attending a one-stop breast care clinic nested within a primary care health facility in sub-Saharan Africa-Zambia.

In Zambia, women with breast symptoms travel through multiple levels of the healthcare system before obtaining a definitive diagnosis. To eradicate this critical barrier to care, we nested a novel breast specialty service platform inside a large public-sector primary healthcare facility in Lusaka, Zambia to offer clinical breast examination, breast ultrasound, and ultrasound-guided core needle biopsy in a one-stop format, tightly linked to referral for treatment. The objective of the study was to determine the life expectancy and survival outcomes of a prospective cohort of women diagnosed with breast cancer who were attended to and followed up at the clinic. The effect of breast cancer stage on prognosis was determined by estimating stage-specific crude survival using the Kaplan-Meier method. Survival analysis was used to estimate mean lifespan according to age and stage at diagnosis. We enrolled 302 women with histologically confirmed breast cancer. The overall 3-year survival was 73%. An increase in patients presenting with early breast cancer and improvements in their survival were observed. Women with early-stage breast cancer had a lifespan similar to the general population, while loss of life expectancy was significant at more advanced stages of disease. Our findings suggest that implementing efficient breast care services at the primary care level can avert a substantial proportion of breast cancer-related deaths. The mitigating factor appears to be stage of disease at the time of diagnosis, the cause of which is multifactorial, with the most influential being delays in the referral process.

Supportive care interventions for cancer patients in low- and middle-income countries (LMICs): a scoping review.

PURPOSE: In high-income countries (HICs), supportive care is often used to assist cancer patients as they seek treatment and beyond. However, in low-and middle-income countries (LMICs), where more than 70% of all cancer-related deaths occur [1], the provision of supportive care has not been assessed. The purpose of this scoping review is to assess the type of supportive care interventions for cancer patients across the cancer care continuum in LMICs. METHODS: We examined published articles reporting on supportive care interventions in LMICs. Following PRISMA guidelines, we performed a systematic search of PubMed, ERIC, CINAHL, and PsycINFO. We limited the scope to original research studies focused on LMICs, studies concerning any type of supportive care intervention for adult cancer patients, from diagnosis, treatment, and post-treatment. RESULTS: Thirty-five studies met the criteria for inclusion in the scoping review. The majority were randomized clinical trials (RCT) or used a quasi-experimental design. The highest number of studies (n = 23) was implemented in the WHO Eastern-Mediterranean region, followed by South-East Asia (n = 6), Africa (n = 4), and Western-Pacific Regions (n = 2). Most studies focused on women's cancers and included interventions for psychosocial support, symptom management, health literacy/education, and patient navigation. CONCLUSIONS: Although we found only a small number of interventions being conducted in these settings, our results suggest that providing different types of supportive services in less-resourced settings, even when health systems are fragmented and fragile, can improve mental health, physical health, and the quality of life (QoL) of cancer patients.

Culture matters: adapting supportive programs for cancer patients in low- and middle-income countries.

The global burden of cancer falls heavily on low- and middle-income countries (LMICs), where there are critical gaps in the provision of supportive care services, which leaves many cancer patients in these settings feeling overwhelmed and unable to manage the psychological effects associated with a cancer diagnosis and the ensuing treatment. In addressing these gaps, we adapted a widely replicated cancer peer mentoring model in the USA to the Viet Nam context. Using the Cultural Adaptation Framework, we examined cultural characteristics affecting three key domains-cognitive information processing, affective-motivational, and environmental-to inform the types of adaptations that are made to the program. We highlight here the major findings in the three domains and the adaptations made. This illustration can inform future efforts to adapt successful programs to different cultural contexts, ensuring that cancer psychosocial programs and activities are acceptable and appropriate to the culture, health system, and resources of the local community and setting.

Maternally Orphaned Children and Intergenerational Concerns Associated With Breast Cancer Deaths Among Women in Sub-Saharan Africa.

IMPORTANCE: Low breast cancer survival in sub-Saharan Africa's young population increases the likelihood that breast cancer deaths result in maternal orphans, ie, children (<18 years) losing their mother. OBJECTIVE: To estimate the number of maternal orphans and their ages for every 100 breast cancer deaths in sub-Saharan African settings during 2014-2019 and to describe family concerns about the orphaned children. DESIGN, SETTING, AND PARTICIPANTS: Deaths occurring between September 1, 2014, and July 1, 2019, in the African Breast Cancer-Disparities in Outcomes (ABC-DO) were examined in a cohort of women diagnosed with breast cancer during 2014-2017 at major cancer treatment hospitals in Namibia, Nigeria, Uganda, and Zambia. The cohort was actively followed up for vital status via a trimonthly mobile phone call to each woman or her next of kin (typically a partner, husband, or child). MAIN OUTCOMES AND MEASURES: The number (Poisson counts) and ages of new orphans at the time of maternal death. RESULTS: This cohort study found that a total of 795 deaths resulted in 964 new maternal orphans, with deaths occurring in women younger than 50 years accounting for 85% of the orphans. For every 100 deaths in women younger than 50 years, there were 210 new orphans (95% CI, 196-225) overall, with country-specific estimates of 189 in Nigerian, 180 in Namibian, 222 in Ugandan, and 247 in Zambian Black women. For every 100 deaths of the women at any age, there were 121 maternal orphans, 17% of whom were younger than 5 years, 32% aged 5 to 9 years, and 51% aged 10 to 17 years at the time of maternal death. In follow-up interviews, families' concerns for children's education and childcare were reported to be exacerbated by the financial expenses associated with cancer treatment. CONCLUSIONS AND RELEVANCE: This study provides evidence that the number of maternal orphans due to breast cancer exceeds the number of breast cancer deaths among women in sub-Saharan Africa. The intergenerational consequences associated with cancer deaths in sub-Saharan Africa appear to be large and support the need for continued action to improve survival.

Minimizing Delays in the Breast Cancer Pathway by Integrating Breast Specialty Care Services at the Primary Health Care Level in Zambia.

PURPOSE: In Zambia, more than two-thirds of female patients with breast cancer present with late-stage disease, leading to high mortality rates. Most of the underlying causes are associated with delays in symptom recognition and diagnosis. By implementing breast care specialty services at the primary health care level, we hypothesized that some of the delays could be minimized. METHODS: In March 2018, we established a breast care specialty clinic for women with symptomatic disease within 1 of the 5 district hospitals in Lusaka. The clinic offers breast self-awareness education, clinical breast examination, breast ultrasound, ultrasound-guided breast biopsy, surgery, referral for chemoradiation, follow-up care, and electronic medical records. RESULTS: Between March 2018 and April 2019, of 1,790 symptomatic women who presented to the clinic, 176 (10%) had clinical and/or ultrasound indications for histologic evaluation. Biopsy specimens were obtained using ultrasound-guided core-needle procedures, all of which were performed on the same day as the initial visit. Of the 176 women who underwent biopsy, 112 (64%) had pathologic findings compatible with a primary breast cancer, and of these, 42 (37%) were early-stage (stage I/II) disease. Surgery for early-stage cancers was performed at the district hospital within 2 weeks of the time of definitive pathologic diagnosis. Patients with advanced disease were referred to the national cancer center for multimodality therapy, within a similar time frame. CONCLUSION: Breast care specialty services for symptomatic women were established in a district-level hospital in a resource-constrained setting in Africa. As a result, the following time intervals were minimized: initial presentation and performance of clinical diagnostics; receipt of a definitive pathologic diagnosis and initiation of surgery; receipt of a definitive pathologic diagnosis and referral.

Breast cancer early detection: A phased approach to implementation.

When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.

Breast cancer patient advocacy: A qualitative study of the challenges and opportunities for civil society organizations in low-income and middle-income countries.

BACKGROUND: Breast cancer advocacy movements, driven by advocate-led civil society organizations (CSOs), have proven to be a powerful force for the advancement of cancer control in high-income countries (HICs). However, although patient advocacy movements are growing in low-income and middle-income countries (LMICs) in response to an increasing cancer burden, the experiences and needs of advocate-led breast cancer CSOs in LMICs is understudied. METHODS: The authors conducted a qualitative study using in-depth interviews and focus group discussions with 98 participants representing 23 LMICs in Eastern Europe, Central Asia, East and Southern Africa, and Latin America. RESULTS: Despite geographic, cultural, and socioeconomic differences, the common themes that emerged from the data across the 3 regions are strikingly similar: trust, knowledge gaps, stigma, sharing experiences, and sustainability. The authors identified common facilitators (training/education, relationship building/networking, third-party facilitators, and communication) and barriers (mistrust, stigma, organizational fragility, difficulty translating HIC strategies) to establishing trust, collaboration, and advancing cancer advocacy efforts. To the authors' knowledge, the current study is the first to describe the role that coalitions and regional networks play in advancing breast cancer advocacy in LMICs across multiple regions. CONCLUSIONS: The findings of the current study corroborate the importance of investing in 3-way partnerships between CSOs, political leaders, and health experts. When provided with information that is evidence-based and resource appropriate, as well as opportunities to network, advocates are better equipped to achieve their goals. The authors propose that support for CSOs focuses on building trust through increasing opportunities for engagement, disseminating best practices and evidence-based information, and fostering the creation of platforms for partnerships and networks.

The Breast Health Global Initiative 2018 Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation: Methods and overview.

BACKGROUND: The Breast Health Global Initiative (BHGI) established a series of resource-stratified, evidence-based guidelines to address breast cancer control in the context of available resources. Here, the authors describe methodologies and health system prerequisites to support the translation and implementation of these guidelines into practice. METHODS: In October 2018, the BHGI convened the Sixth Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation. The purpose of the summit was to define a stepwise methodology (phased implementation) for guiding the translation of resource-appropriate breast cancer control guidelines into real-world practice. Three expert consensus panels developed stepwise, resource-appropriate recommendations for implementing these guidelines in low-income and middle-income countries as well as underserved communities in high-income countries. Each panel focused on 1 of 3 specific aspects of breast cancer care: 1) early detection, 2) treatment, and 3) health system strengthening. RESULTS: Key findings from the summit and subsequent article preparation included the identification of phased-implementation prerequisites that were explored during consensus debates. These core issues and concepts are key components for implementing breast health care that consider real-world resource constraints. Communication and engagement across all levels of care is vital to any effectively operating health care system, including effective communication with ministries of health and of finance, to demonstrate needs, outcomes, and cost benefits. CONCLUSIONS: Underserved communities at all economic levels require effective strategies to deploy scarce resources to ensure access to timely, effective, and affordable health care. Systematically strategic approaches translating guidelines into practice are needed to build health system capacity to meet the current and anticipated global breast cancer burden.

Challenges, Opportunities, and Priorities for Advancing Breast Cancer Control in Zambia: A Consultative Meeting on Breast Cancer Control.

In 2016, the Zambian government made cancer control a national priority and released a National Cancer Control Strategic Plan for 2016 to 2021, which focuses on malignancies of the breast, cervix, and prostate, and retinoblastoma. The plan calls for a collective reduction in the cancer burden by 50%. In support of this vision, Susan G. Komen sponsored a consultative meeting in Lusaka, Zambia, in September 2017 to bring together the country's main breast cancer stakeholders and identify opportunities to improve breast cancer control. The recommendations generated during the discussions are presented. There was general agreement that the first step toward breast cancer mortality reduction should consist of implementation of early detection service platforms focused on women who are symptomatic. Participants also agreed that the management of all components of the national breast cancer control program should be integrated and led by the Ministry of Health. As much as possible, early detection and treatment services presently offered by the Cervical Cancer Prevention Program of Zambia and Cancer Diseases Hospital should be leveraged. Efforts are under way through multiple stakeholders to implement the following recommendations: development of national guidelines for the early diagnosis of breast cancer, training of breast surgeons, implementation of early detection and surgical treatment service platforms at the district-hospital level, and epidemiologic research, including the improvement of electronic recording mechanisms.

Global analysis of metastatic breast cancer policy gaps and advocacy efforts across the patient journey.

Metastatic breast cancer (mBC) is an area with high unmet need across the world. Despite significant progress to meet patient need, current breast cancer (BC) policies fail to recognize the unique challenges of patients who are further along the cancer patient journey. This analysis aims to understand BC/mBC policy development at a global level and identify opportunities for further development. A comprehensive analysis of National Cancer Control Plans (NCCPs) policies and programs was conducted across 16 countries, which represent a diverse range of healthcare systems, economies and geographic regions. Examples of promising practices, implemented or initiated by civil society, are provided to demonstrate successful methods to address the identified policy gaps. The analysis finds that disparities in BC policy development exist across and within countries. Progress in BC policy is fragmented and skewed towards the early part of the patient journey e.g. awareness and stakeholder education, with key gaps remaining in diagnosis and patient identification. In addition, access to innovative mBC treatments, ongoing support and palliative care remain a challenge, while care coordination is limited due to inefficient referrals. Although government and policymaker action is fundamental, collaboration between different stakeholders is imperative to address unmet needs of BC/mBC patients alike. Policy initiatives and promising practices that demonstrate successful multi-stakeholder engagement can be replicated or used to inform further advocacy and policy development with the aim to address patient unmet needs.

Cervical and female breast cancers in the Americas: current situation and opportunities for action.

OBJECTIVE: To understand better the current regional situation and public health response to cervical cancer and female breast cancer in the Americas. METHODS: Data on cervical cancer and female breast cancers in 33 countries, for the period from 2000 to the last year with available data, were extracted from the Pan American Health Organization (PAHO) Regional Mortality Database and analysed. Changes in mortality rates over the study period - in all countries except those with small populations and large fluctuations in time-series mortality data - were calculated using Poisson regression models. Information from the PAHO Country Capacity Survey on noncommunicable diseases was also analysed. FINDINGS: The Bahamas, Trinidad and Tobago and Uruguay showed relatively high rates of death from breast cancer, whereas the three highest rates of death from cervical cancer were observed in El Salvador, Nicaragua and Paraguay. Several countries - particularly Paraguay and Venezuela - have high rates of death from both types of cancer. Although mortality from cervical cancer has generally been decreasing in the Americas, decreases in mortality from breast cancer have only been observed in a few countries in the Region of the Americas. All but one of the 25 countries in the Americas included in the PAHO Country Capacity Survey reported having public health services for the screening and treatment of breast and cervical cancers. CONCLUSION: Most countries in the Americas have the public health capacity needed to screen for - and treat - breast and cervical cancers and, therefore, the potential to reduce the burden posed by these cancers.

Disparities in breast cancer mortality trends in a middle income country.

In recent decades, breast cancer cases have increased steadily worldwide. However, the increases do not hold across all demographics and breast cancer cases in low and middle income countries have increased much faster than the global trend. Colombia is not an exception. Breast cancer was the most frequent tumor and the second cause of cancer-related deaths in women in 2008, with an estimated of 6,700 new cases and 2,100 deaths. We present here an analysis of breast cancer mortality rates and trends in Colombia, over the period 1985-2008. We studied overall and age-specific changes in breast cancer mortality using change-point Poisson regression models. Between 1985 and 2008, there were 32,375 breast cancer deaths in women in Colombia. Breast cancer mortality increased since 1985, although the annual increase varied between age groups and socioeconomic levels. Only in women aged 45-64 years old that live in areas of high socioeconomic levels, breast cancer mortality was stable or decreasing. Hence, successful cancer control is possible in middle income countries, as shown by the progress observed in certain groups. The development of an integrated strategy of early detection and early access to proper treatment, suitable for areas with limited resources, is an urgent necessity.

Childhood factors associated with mammographic density in adult women.

Growth and development factors could contribute to the development of breast cancer associated with an increase in mammographic density. This study examines the influence of certain childhood-related, socio-demographic and anthropometric variables on mammographic density in adult woman. The study covered 3574 women aged 45-68 years, participating in breast cancer-screening programmes in seven Spanish cities. Based on a craniocaudal mammogram, blind, anonymous measurement of mammographic density was made by a single radiologist, using Boyd's semiquantitative scale. Data associated with the early stages of life were obtained from a direct survey. Ordinal logistic regression and generalised linear models were employed to estimate the association between mammographic density and the variables covered by the questionnaire. Screening programme was introduced as a random effects term. Age, number of children, body mass index (BMI) and other childhood-related variables were used as adjustment variables, and stratified by menopausal status. A total of 811 women (23%) presented mammographic density of over 50%, and 5% of densities exceeded 75%. Our results show a greater prevalence of high mammographic density in women with low prepubertal weight (OR: 1.18; 95% CI: 1.02-1.36); marked prepubertal height (OR: 1.25; 95% CI: 0.97-1.60) and advanced age of their mothers at their birth (>39 years: OR: 1.28; 95% CI: 1.03-1.60); and a lower prevalence of high mammographic density in women with higher prepubertal weight, low birth weight and earlier menarche. The influence of these early-life factors may be explained by greater exposure to hormones and growth factors during the development of the breast gland, when breast tissue would be particularly susceptible to proliferative and carcinogenic stimulus.

Alcohol, tobacco, and mammographic density: a population-based study.

Mammographic density (MD), or the proportion of the breast with respect to its overall area that is composed of dense tissue, is a strong risk factor for breast cancer. Studies support a positive association of mammographic density and alcohol drinking. This was a cross-sectional multicenter study based on 3584 women, aged 45-68 years, recruited from seven screening centers within the Spanish breast cancer screening program network. The association between MD, alcohol consumption and tobacco use was evaluated by using ordinal logistic models with random center-specific intercepts. We found a weak positive association between current alcohol intake and higher MD, with current alcohol consumption increasing the odds of high MD by 13% (OR = 1.13; 95% CI 0.99-1.28) and high daily grams of alcohol being positively associated with increased MD (P for trend = 0.045). There were no statistically significant differences in MD between smokers and non-smokers. Nevertheless, increased number of daily cigarettes and increased number of accumulated lifetime cigarettes were negatively associated with high MD (P for trend 0.017 and 0.021). The effect of alcohol on MD was modified by menopausal status and tobacco smoking: whereas, alcohol consumption and daily grams of alcohol were positively associated with higher MD in postmenopausal women and in women who were not currently smoking, alcohol consumption had no effect on MD in premenopausal women and current smokers. Our results support an association between recent alcohol consumption and high MD, characterized by a modest increase in risk at low levels of current consumption and a decrease in risk among heavier drinkers. Our study also shows how the effects of alcohol in the breast can be modified by other factors, such as smoking.

Decline in age at menarche among Spanish women born from 1925 to 1962.

BACKGROUND: While the timing of reproductive events varies across populations, a downward trend in age at menarche has nevertheless been reported in most of the developed world over the past century. Given the impact of change in age at menarche on health conditions, this study sought to examine secular trends in age at menarche among women living in Navarre (Northern Spain) who participated in a population-based breast cancer screening programme. METHODS: The study was based on 110545 women born from 1925 to 1962. Trends were tested using a linear regression model, in which year of birth was entered continuously as the predictor and age at menarche (years) as the response variable, using size of town and region of birth as covariates. RESULTS: Among women born in Navarre between 1925 and 1962, age at menarche declined steadily from an average of 13.72 years in the 1925-1929 birth-cohorts to 12.83 years in the 1958-1962 birth-cohorts. Controlling for size of town or city of birth, age at menarche declined by an average of 0.132 years every 5 years over the period 1925-1962. This decline was greater in women born in rural versus urban settings. Trends were also different among regions of birth. CONCLUSION: We report a population-based study showing a downward trend in age of onset of menarche among Spanish women born in the period 1925-1962, something that is more pronounced among women born in rural settings and varies geographically.

Age-specific breast, uterine and ovarian cancer mortality trends in Spain: changes from 1980 to 2006.

INTRODUCTION: Cancers of the breast, uterus and ovary are responsible for 30% of the cancer deaths in Spanish women. In recent decades, Spain has experienced important socioeconomic transformations, which may have affected mortality trends. We present the current situation of mortality in Spain due to cancers of the breast, uterus and ovary, as well as trends over 1980-2006. METHODS: Data on population and deaths due to cancers of the breast, uterus and ovary were obtained from records of the National Statistics Institute. Overall and age-specific changes in mortality of these tumors were studied using change-point Poisson regression models. RESULTS: Breast cancer was responsible for more than 140,000 deaths of females in 1980-2006. Trend analysis of breast cancer mortality of women of all ages showed that rates increased 2.9% annually until 1992 (95% confidence interval (CI)=2.5, 3.3). After 1992, mortality declined steadily at a rate of -2.1% per year (95% CI=-2.4, -1.8). The number of deaths due to cancers of the uterus was 49,287 between the years 1980 and 2006. Uterine cancer mortality registered a steady decrease of -1.9% every year since 1980 (95% CI=-2.1, -1.8). Ovarian cancer caused 36,157 deaths during the same period, with rates in women older than 50 years more than ten-fold those of younger women. Trend analysis showed a sharp increase of mortality up to 1998 (4.4% annually; 95% CI=3.9, 4.8) followed by a stabilization. CONCLUSION: The downturn observed in mortality for these tumors mainly reflects improved survival as a result of earlier diagnosis and better cancer treatments. Cancer management is moving in the right direction in Spain.

Municipal distribution of ovarian cancer mortality in Spain.

BACKGROUND: Spain was the country that registered the greatest increases in ovarian cancer mortality in Europe. This study describes the municipal distribution of ovarian cancer mortality in Spain using spatial models for small-area analysis. METHODS: Smoothed relative risks of ovarian cancer mortality were obtained, using the Besag, York and Molliè autoregressive spatial model. Standardised mortality ratios, smoothed relative risks, and distribution of the posterior probability of relative risks being greater than 1 were depicted on municipal maps. RESULTS: During the study period (1989-1998), 13,869 ovarian cancer deaths were registered in 2,718 Spanish towns, accounting for 4% of all cancer-related deaths among women. The highest relative risks were mainly concentrated in three areas, i.e., the interior of Barcelona and Gerona (north-east Spain), the north of Lugo and Asturias (north-west Spain) and along the Seville-Huelva boundary (in the south-west). Eivissa (Balearic Islands) and El Hierro (Canary Islands) also registered increased risks. CONCLUSION: Well established ovarian cancer risk factors might not contribute significantly to the municipal distribution of ovarian cancer mortality. Environmental and occupational exposures possibly linked to this pattern and prevalent in specific regions, are discussed in this paper. Small-area geographical studies are effective instruments for detecting risk areas that may otherwise remain concealed on a more reduced scale.

Gene signaling pathways mediating the opposite effects of prepubertal low-fat and high-fat n-3 polyunsaturated fatty acid diets on mammary cancer risk.

In rats, prepubertal exposure to low-fat diet containing n-3 polyunsaturated fatty acids (PUFA) reduces mammary cell proliferation, increases apoptosis, and lowers risk of mammary tumors in adulthood, whereas prepubertal high-fat n-3 PUFA exposure has opposite effects. To identify signaling pathways mediating these effects, we performed gene microarray analyses and determined protein levels of genes related to mammary epithelial cell proliferation. Nursing female rats and rat pups were fed low-fat (16% energy from fat) or high-fat (39% energy from fat) n-3 or n-6 PUFA diets between postnatal days 5 and 24. cDNA gene expression microarrays were used to identify global changes in the mammary glands of 50-day-old rats. Differences in gene expression were confirmed by real-time quantitative PCR, and immunohistochemistry was used to assess changes in the peroxisome proliferator-activated receptor gamma and cyclin D1 levels. DNA damage was determined by 8-hydroxy-2'-deoxyguanosine assay. Expressions of the antioxidant genes thioredoxin, heme oxygenase, NADP-dependent isocitrate dehydrogenase, and metallothionein III, as well as peroxisome proliferator-activated receptor gamma protein, were increased in the mammary glands of 50-day-old rats prepubertally fed the low-fat n-3 PUFA diet. Prepubertal exposure to the high-fat n-3 PUFA diet increased DNA damage and cyclin D1 protein and reduced expression of BRCA1 and cardiotrophin-1. Reduction in mammary tumorigenesis among rats prepubertally fed a low-fat n-3 PUFA diet was associated with an up-regulation of antioxidant genes, whereas the increase in mammary tumorigenesis in the high-fat n-3 PUFA fed rats was linked to up-regulation of genes that induce cell proliferation and down-regulation of genes that repair DNA damage and induce apoptosis.

Maternal flaxseed diet during pregnancy or lactation increases female rat offspring's susceptibility to carcinogen-induced mammary tumorigenesis.

Flaxseed contains several dietary components that have been linked to low breast cancer risk; i.e., n-3 polyunsaturated fatty acids (PUFAs), lignans and fiber, but it also contains detectable levels of cadmium, a heavy metal that activates the estrogen receptor (ER). Since estrogenic exposures early in life modify susceptibility to develop breast cancer, we wondered whether maternal dietary intake of 5% or 10% flaxseed during pregnancy or lactation (between postpartum days 5 and 25) might affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in the rat offspring. Our data indicated that both in utero and postnatal 5% and 10% flaxseed exposures shortened mammary tumor latency, and 10% flaxseed exposure increased tumor multiplicity, compared to the controls. Further, when assessed in 8-week-old rats, in utero 10% flaxseed exposure increased lobular ER-alpha protein levels, and both in utero and postnatal flaxseed exposures dose-dependently reduced ER-beta protein levels in the terminal end buds (TEBs) lobules and ducts. Exposures to flaxseed did not alter the number of TEBs or affect cell proliferation within the epithelial structures. In a separate group of immature rats that were fed 5% defatted flaxseed diet (flaxseed source different than in the diets fed to pregnant or lactating rats) for 7 days, cadmium exposure through the diet was six-fold higher than allowed for humans by World Health Organization, and cadmium significantly accumulated in the liver and kidneys of the rats. It remains to be determined whether the increased mammary cancer in rats exposed to flaxseed through a maternal diet in utero or lactation was caused by cadmium present in flaxseed, and whether the reduced mammary ER-beta content was causally linked to increased mammary cancer risk among the offspring.