Breast Cancer Morbidity Research Articles

Women at High Risk for Breast Cancer--What the Primary Care Provider Needs to Know

Until recently, the assessment made by the primary care provider regarding screening for breast cancer was generally limited to decisions about when to initiate mammography. Early diagnosis was stressed as the best protection against breast cancer morbidity. However, there have been recent developments in the ability to predict and modify breast cancer risk. It is therefore important for the primary care provider to be able to identify women at higher risk for breast cancer and be familiar with issues regarding screening and risk reduction. Recent data regarding the evaluation of breast cancer risk, newer screening strategies for high-risk women, and medical and surgical approaches to reduce breast cancer risk and are discussed in this article.

Challenging patient populations in breast cancer: Taxane resistance and triple‐negative receptor subtype

AbstractOver the last decade the introduction of the taxanes and several targeted therapies have led to an improvement in breast cancer morbidity and mortality. However, several groups of patients, including patients with taxane‐resistant, multidrug resistant, and estrogen‐negative, progesterone‐negative, and HER2/neu receptor‐negative tumors, have now emerged that present challenges to clinicians as they strive to improve the outcomes for patients with breast cancer. This review examines the state of knowledge at the time of writing regarding the mechanisms of taxane resistance and the natural history of triple‐negative disease. Strategies for overcoming taxane resistance and the improving clinical outcomes for these groups of patient are discussed.

A time for creative collaboration

A time for creative collaboration

Breast and Cervical Cancer Screening Among Latinas Attending Culturally Specific Educational Programs

Latinas in the United States have higher morbidity and mortality rates for breast and cervical cancers (compared with non-Latina Whites), often due to lower screening rates. A community-based participatory research (CBPR) approach could help to improve screening rates by creating a culturally customized educational program for Latino men and women addressing low knowledge, gender roles, and spirituality. This study was designed to assess the effectiveness of a culturally customized program (Esperanza y Vida [Hope and Life]) in increasing breast and cervical cancer screening among Latinas, and to examine how screening rates related to changes in cancer knowledge, differences in ethnic origins, and geographic location. Participants were recruited to attend either a breast and cervical (intervention) or diabetes (control) education program, within a randomized plan. Sixty-nine programs (44 intervention; 25 control) were conducted in Arkansas (AR; n = 39) and New York City (NYC; n = 30) with a total of 847 Latino men and women. Telephone follow-up data were collected on 49% of the women who consented to being contacted 2 months postintervention. At the 2-month follow-up call, screening rates were significantly higher for the intervention versus the control group for clinical breast examination (CBE; 48% vs. 31%; adjusted odds ratio [aOR], 2.2; 95% confidence interval [CI], 1.1-4.2), breast self-examination (45% vs. 27%; aOR, 2.3; 95% CI, 1.1-5.0), and Pap testing (51% vs. 30%; aOR, 3.9; 95% CI, 1.1-14.1), but not for mammography (67% vs. 58%; aOR, 0.7; 95% CI, 0.1-3.6). The aORs accounted for the significant effects of study site (AR vs. NYC) and marital status. Esperanza y Vida has the potential to reduce health disparities in breast and cervical cancer morbidity and mortality rates through increasing cancer screening and thereby increasing early detection.

Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression

Obesity is a recently established risk factor for breast cancer incidence and mortality. A characteristic of obesity is elevated circulating levels of adipocyte-derived hormone leptin. Evidence indicates that leptin plays an important role in mammary tumor formation; however, the mechanisms involved are poorly understood. Toward better defining the role of leptin in breast cancer, we describe the identification of leptin-regulated genes in hormone-responsive Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells using a microarray system. More than 64 leptin-regulated genes were identified including those for growth factors, cell cycle regulators, extracellular matrix (ECM) proteins, and genes associated with metastasis. Cell cycle genes up-regulated by leptin include cyclins D and G, cyclin-dependent kinase 2, p21, p27, and p16. Leptin suppressed the expression of transforming growth factor-beta , a cell cycle suppressor. Determining the significance of this effect, treatment of MCF-7 cells with TGFB1 abrogated leptin-stimulated proliferation. Leptin up-regulated the expression of connective tissue growth factor, villin 2, and basigin, factors that are associated with ECM and are known to impact tumor growth. Finally, leptin induced the expression of anti-apoptotic genes BCL2 and survivin, and reduced the expression of apoptotic genes. The effect of leptin on MCF-7 survival was evaluated via TUNEL assay and demonstrated a sixfold reduction in apoptosis in leptin-treated cells, compared with controls. These data suggest leptin promotes mammary tumor growth through multiple mechanisms, including regulating the cell cycle, apoptosis, and by modulating the extracellular environment. The identification of leptin-regulated genes begins to provide mechanistic links into the relationship between obesity and breast cancer incidence and morbidity.

Nanotechnology for breast cancer therapy

Breast cancer is the field of medicine with the greatest presence of nanotechnological therapeutic agents in the clinic. A pegylated form of liposomally encapsulated doxorubicin is routinely used for treatment against metastatic cancer, and albumin nanoparticulate chaperones of paclitaxel were approved for locally recurrent and metastatic disease in 2005. These drugs have yielded substantial clinical benefit, and are steadily gathering greater beneficial impact. Clinical trials currently employing these drugs in combination with chemo and biological therapeutics exceed 150 worldwide. Despite these advancements, breast cancer morbidity and mortality is unacceptably high. Nanotechnology offers potential solutions to the historical challenge that has rendered breast cancer so difficult to contain and eradicate: the extreme biological diversity of the disease presentation in the patient population and in the evolutionary changes of any individual disease, the multiple pathways that drive disease progression, the onset of 'resistance' to established therapeutic cocktails, and the gravity of the side effects to treatment, which result from generally very poor distribution of the injected therapeutic agents in the body. A fundamental requirement for success in the development of new therapeutic strategies is that breast cancer specialists-in the clinic, the pharmaceutical and the basic biological laboratory-and nanotechnologists-engineers, physicists, chemists and mathematicians-optimize their ability to work in close collaboration. This further requires a mutual openness across cultural and language barriers, academic reward systems, and many other 'environmental' divides. This paper is respectfully submitted to the community to help foster the mutual interactions of the breast cancer world with micro- and nano-technology, and in particular to encourage the latter community to direct ever increasing attention to breast cancer, where an extraordinary beneficial impact may result. The paper initiates with an introductory overview of breast cancer, its current treatment modalities, and the current role of nanotechnology in the clinic. Our perspectives are then presented on what the greatest opportunities for nanotechnology are; this follows from an analysis of the role of biological barriers that adversely determine the biological distribution of intravascularly injected therapeutic agents. Different generations of nanotechnology tools for drug delivery are reviewed, and our current strategy for addressing the sequential bio-barriers is also presented, and is accompanied by an encouragement to the community to develop even more effective ones.

Preoperative assessment enables the early diagnosis and successful treatment of lymphedema

The incidence of breast cancer (BC)-related lymphedema (LE) ranges from 7% to 47%. Successful management of LE relies on early diagnosis using sensitive measurement techniques. In the current study, the authors demonstrated the effectiveness of a surveillance program that included preoperative limb volume measurement and interval postoperative follow-up to detect and treat subclinical LE. LE was identified in 43 of 196 women who participated in a prospective BC morbidity trial. Limb volume was measured preoperatively and at 3-month intervals after surgery. If an increase>3% in upper limb (UL) volume developed compared with the preoperative volume, then a diagnosis of LE was made, and a compression garment intervention was prescribed for 4 weeks. Upon reduction of LE, garment wear was continued only during strenuous activity, with symptoms of heaviness, or with visible swelling. Women returned to the 3-month interval surveillance pathway. Statistical analysis was a repeated-measures analysis of variance by time and limb (P<or=.001) comparing the LE cohort with an age-matched control group. The time to onset of LE averaged 6.9 months postoperatively. The mean (+/-standard deviation) affected limb volume increase was 83 mL (+/-119 mL; 6.5%+/-9.9%) at LE onset (P=.005) compared with baseline. After the intervention, a statistically significant mean 48 mL (+/-103 mL; 4.1%+/-8.8%) volume decrease was realized (P<.0001). The mean duration of the intervention was 4.4 weeks (+/-2.9 weeks). Volume reduction was maintained at an average follow-up of 4.8 months (+/-4.1 months) after the intervention. A short trial of compression garments effectively treated subclinical LE.

THE ROLE OF VARIOUS MODALITIES IN BREAST IMAGING

Breast cancer is the most common type of cancer in women worldwide. Mammography is considered the "gold standard" in the evaluation of the breast from an imaging perspective. Apart from mammography, ultrasound examination and magnetic resonance imaging are being offered as adjuncts to the preoperative workup. Recently, other new modalities like positron emission tomography, 99mTc-sestamibi scintimammography, and electrical impedance tomography (EIT) are also being offered. However, there is still controversy over the most appropriate use of these new modalities. Based on the literature, this review evaluates the role of various modalities used in the screening and diagnosis of breast cancer. Based on relevant literatures this article gives an overview of the old and new modalities used in the field of breast imaging. A narrative literature review of all the relevant papers known to the authors was conducted. The search of literatures was done using pubmed and ovid search engines. Additional references were found through bibliography reviews of relevant articles. It was clear that though various new technics and methods have emerged, none have substituted mammography and it is still the only proven screening method for the breast as of date. From the literature it is clear that apropos modern radiology's impact on diagnosis, staging and patient follow-up, only one imaging technique has had a significant impact on screening asymptomatic individuals for cancer i.e.; low-dose mammography. Mammography is the only screening test proven in breast imaging. Positron emission tomography (PET) also plays an important role in staging breast cancer and monitoring treatment response. As imaging techniques improve, the role of imaging will continue to evolve with the goal remaining a decrease in breast cancer morbidity and mortality. Progress in the development and commercialisation of EIT breast imaging system will definitely help to promote other systems and applications based on the EIT and similar visualization methods. Breast ultrasound and breast magnetic resonance imaging (MRI) are frequently used adjuncts to mammography in today's clinical practice and these techniques enhance the radiologist's ability to detect cancer and assess disease extent, which is crucial in treatment planning and staging.

Electro-endocrine combination therapy for aggressive breast tumors

Obesity is an epidemic in the US and an established risk factor for breast cancer incidence and morbidity. In obese patients breast cancer is commonly more aggressive and associated with poor prognosis. The goal of our research is to develop safe and efficient novel therapies to treat aggressive breast tumors, like those in obese patients. To enhance drug uptake we intend to develop electro-endocrine therapy, an electrically mediated hormone (endocrine) delivery system. In this study, we optimize parameters for electrical pulses and tamoxifen (anti-hormone drug) dosages in an in vitro model of breast cancer, as these parameters vary for each cell type. For this purpose, MCF-7 human breast adenocarcinoma cells were used. Results of our experiments show that treatment of electroporation combined with tamoxifen has an enhanced effect on suppressing tumor cell growth compared to tamoxifen treatment alone. The long-term goal is to translate application of this method to clinical practice.

RNA interference of ecto-5′-nucleotidase (CD73) inhibits human breast cancer cell growth and invasion

Metastasis is a leading cause of mortality and morbidity in breast cancer. Recently, dramatic overexpression of ecto-5'-nucleotidase (CD73), a glycosylphosphatidylinositol-anchored cell surface protein has been found in estrogen receptor-negative [ER (-)] breast cancer cell lines and in clinical samples. In this study, CD73 small interfering RNA (siRNA) plasmid was constructed and stably transfected into breast cancer cell MB-MDA-231 to determine the role of CD73 in breast cancer metastasis and the possible mechanism. Our study demonstrates that CD73 siRNA effectively inhibits CD73 gene expression at mRNA and protein level in MB-MDA-231 cells, leading to in vivo and in vitro growth suppression, prevention of adhesion to extracellular matrix (ECM), and inhibition of invasion and migration. These properties correlate with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 expression and activity as well as reduction of epidermal growth factor receptor (EGFR) expression. Demonstration of the role of CD73 in breast cancer may lead to new targeted therapies for breast cancer.

Hypocalcemia induced by bisphophonates in cancer patients with vitamin D deficiency

19644 Background: The use of bisphosphonates for treatment of hypercalcemia, bone pain and reduction of skeletal morbidity in metastatic breast cancer is increasing. Moreover, vitamin D deficiency is commonly associated with cancer. Hypocalcemia has been reported following IV bisphosphonate use. Methods: We present the clinical and lab findings in 6 cases of bisphosphonate-induced hypocalcemia, caused by unmasked vitamin D deficiency. Results: Our 1st patient was diagnosed with breast cancer and developed metastases 6yrs later. She was given Zolendronic acid 4 mg IV with a baseline calcium level (Ca) of 9.7 mg/dl, normal albumin, and elevated alkaline phosphatase. 3 days later, she developed symptomatic severe hypocalcemia with tetany: Ca dropped to 6.1 mg/dl with recovery. After her 2nd dose of Zolendronic acid, Ca dropped again to 6 mg/dl with normal albumin, intact parathyroid hormone (PTH) of 637 pg/ml (range 10–65) and 25-hydroxy vitamin D levels (25-OHD) of 4 ng/ml (range 20–100). Our 2nd patient presented with metastatic breast cancer and was treated with Zolendronic acid for hypercalcemia with a baseline Ca of 13 mg/dl, PTH-related protein of 2.8 pmol/l (range &lt;1.8) and PTH of 7 pg/ml. She then developed hypocalcemia with corrected Ca of 7.7 mg/dl and 25-OHD of 13 ng/ml. Our 3rd patient with breast cancer was also treated with Zolendronic acid for bone metastases and hypercalcemia. She then presented with symptomatic hypocalcemia: ionized Ca level of 1.09 mmol/l (range 1.13–1.32), PTH of 211 pg/ml and 25-OHD of 13 ng/ml. Our other 3 cases had similar presentations to the above and will be discussed in detail. All 6 cases were treated with ergocalciferol and long-term oral calcium and vitamin D therapy. All of our cases presented with symptomatic hypocalcemia with vitamin D levels less than 30ng/mL. Conclusions: Since bisphosphonate use is increasing in cancer patients and vitamin D deficiency is not an uncommon finding in this population, consideration should be given to routine checking of 25-OHD levels before initiating treatment with bisphosphonates and supplementing with calcium and vitamin D when necessary (&lt;30ng/mL). This could potentially prevent further morbidity. Further prospective studies would be needed for early replacement with vitamin D and calcium in those with vitamin D deficiency. No significant financial relationships to disclose.

Health conditions of the population and some outcomes of the international collaborative research programs in the Semipalatinsk region of Kazakhstan

From 1949 to 1989, about 450 nuclear explosions were conducted at the Semipalatinsk Nuclear Test Site, Kazakhstan, which resulted in substantial levels of radiation exposure of neighboring settlements and their residents. The incidence of oncological diseases in the East Kazakhstan region, including Semipalatinsk, are very high in comparison to other regions of Kazakhstan. For example, the incidence of breast cancer in East Kazakhstan is 1.5-fold higher in comparison to the average rate of breast cancer in Kazakhstan and is 2.5-fold higher than that in South Kazakhstan. We documented the prevalence of breast cancer morbidity among patients from zones of extreme radiation risk and maximal radiation risk. Our results show an apparently strong association between fallout exposure and the prevalence of thyroid diseases. After the Tokyo International Conference in 1999, in which the health problems of populations living close to the Semipalatinsk Nuclear Test Site and methods of its rehabilitation were discussed, the Japanese government, JICA, scientists and NGO from Japan provided a really valuable support for the Semipalatinsk region of Kazakhstan. Modern medical equipment was granted by the Japanese government. Installed Telemedicine was very valuable for consultation of 1822 patients. Screening program covered more than 34,000 inhabitants from exposed and non-exposed villages. Collaborative research projects with scientists from Japan, including Nagasaki University, allowed us to successfully conduct epidemiological research projects in the Semipalatinsk region of Kazakhstan and considerably improve diagnosis and treatment of many diseases related to consequences of nuclear weapons testing.

Screening, Prevention, Detection, and Treatment of Cancer Therapy-Induced Bone Loss in Patients With Breast Cancer

To identify protocols to screen, detect, prevent, and treat cancer therapy-induced bone loss resulting in osteoporosis in patients with breast cancer. Published books and articles. Normal bone remodeling is affected by hormonal stimulation. Breast cancer therapies target hormones that promote cancer cell growth. Chemotherapy regimens and hormone ablation may cause ovarian failure, resulting in decreased hormone levels. A decrease in hormones, in estrogen- and progesterone-positive and -negative patients, introduces an environment for decreased bone remodeling, which may result in thinning bone and osteoporosis. The acceleration of bone loss leading to osteoporosis can result in higher fracture rates among breast cancer survivors. With proper use of screening tools, patient education, and advice about lifestyle changes, all prior to cancer treatment, healthcare professionals may decrease or prevent bone loss in patients with breast cancer. Doing so minimizes healthcare costs and decreases morbidity and mortality rates in breast cancer survivors. As more individuals diagnosed with breast cancer are surviving for extended periods of time, oncology nurses are providing long-term follow-up care. Part of the care should include proper screening and patient education for healthier recovery and prevention of further healthcare complications as a result of cancer treatment.

Research institute for nurse scientists responds to the challenge to expand and strengthen research focused on breast cancer in African American women

In an era where scientifically derived 'evidence' is used as a basis for nursing practice, it is imperative that nurses have a breadth of knowledge relative to the fundamentals of nursing science; knowledge of the current standards of nursing and medical practice; and knowledge of the characteristics, needs, concerns, and challenges of diverse consumer and patient population groups. Yet, while a significant body of 'evidence' that describes the experiences and needs of African American women across the breast care continuum has been generated, research suggests that there is a need to expand and strengthen this body of science. This report presents an overview of a decade of research focused on breast cancer among African American women and describes an initiative funded by the Susan G. Komen Breast Cancer Foundation to expand and strengthen nursing science that aims to reduce and/or eliminate excess breast cancer morbidity and mortality among African American women. Cancer 2007. (c) 2006 American Cancer Society.

Comparison of three different mediastinal radiotherapy techniques in female patients: Impact on heart sparing and dose to the breasts

Background and purpose To study different radiotherapy techniques for female patients with mediastinal target volumes. Especially in highly curable diseases such as lymphoma, long-term survivors might develop late cardiac damage and radiation-induced second cancer. Patients and methods Planning CT scans were obtained in eight cases. We contoured the clinical target volume (three different scenarios with or without lower mediastinum and hili) and organs at risk and compared standard 6 MV ap–pa opposed fields to a 3D conformal 4-field technique and a 7-field step-and-shoot IMRT technique and evaluated DVHs for each structure. The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany). Results Target volume coverage did not improve significantly with 4-field or IMRT techniques. However, IMRT resulted in better dose reduction to the heart than the other techniques. The median heart dose (intermediately sized target volume) was 98% (95–100) with ap–pa fields, 56% (52–79) with the 4-field technique, and 39% (36–65) with IMRT, for example ( p < 0.05). Better heart sparing was achieved at all dose levels down to the 15% isodose. The median maximum dose to the breasts was lowest with IMRT. The breast volume receiving low doses (15% or less), however, was highest with IMRT. There was also a disadvantage in mean lung dose. Conclusions IMRT might result in a reduced cardiac complication risk. In younger females, however, this advantage might be offset by the risk of breast cancer. The best technique for a given patient depends on age, comorbidity, and the individual risk estimates for breast cancer and cardiac morbidity, respectively.

Chapter 8: The SPECTRUM Population Model of the Impact of Screening and Treatment on U.S. Breast Cancer Trends From 1975 to 2000: Principles and Practice of the Model Methods

This stochastic simulation model was developed to estimate the impact of screening and treatment diffusion on U.S. breast cancer mortality between 1975 and 2000. We use an event-driven continuous-time state transition model. Women who are destined to develop breast cancer may be screen detected, present with symptoms, or die of other causes before cancer is diagnosed. At presentation, the cancer has a stage assigned on the basis of mode of detection. Cancers are assumed to be estrogen receptor (ER) positive or negative. Data on screening and treatment diffusion are based on national datasets; other parameters are based on a synthesis of the evidence available in the literature. The model is calibrated to predict incidence and stage distribution (in situ, local, regional, and distant). Other than screening or treatment, background events that affect mortality are not explicitly modeled but are captured in the deviation between model projections of mortality trends and actual trends. We assume that: 1) tumors progress more slowly in older age groups, 2) screen- and clinically detected disease have the same survival conditional on age and stage, 3) women do not die of breast cancer within the "lead time" period, 4) screening benefits are captured by shifts in stage at diagnosis, 4) tamoxifen benefits only ER-positive women, and 5) preclinical sojourn time and dwell times in each of the clinical stages are stochastically independent. Dissemination of screening and therapeutic advances had a substantial impact on mortality trends. We estimate that, by the year 2000, diffusion of screening lowered mortality by 12.4% and treatment improvements and dissemination lowered mortality by 14.6%. Models such as this one can be useful to translate clinical trial findings to general populations. This model can also be used inform policy debates about how to best achieve targeted reductions in breast cancer morbidity and mortality.

Analysis of skeletal morbidity in breast cancer (BC) patients treated with zoledronic acid (Zol) or placebo: Time to first pathologic fracture

10639 Background: We have previously reported that Zol significantly delayed time to first skeletal-related event (SRE) compared with placebo in BC patients with bone metastases in a multicenter randomized trial conducted in Japan. Patients with bone metastases from BC suffer from a range of skeletal complications, including pathologic fractures that can dramatically decrease mobility and adversely affect patient autonomy and quality of life. Methods: 228 women with bone metastases were randomized to 4 mg Zol (n = 114) or placebo (n = 114) every 4 weeks for 1 year. Time to first skeletal event was estimated using the Kaplan-Meier method for all individual types of event. Median time to individual skeletal events was not reached in either treatment group; therefore, data are presented as the incidence at 1 year, and the log-rank P value is from the Kaplan-Meier estimate of time to first event. Results: Median time to first SRE (including hypercalcemia) was not reached in the Zol group versus 360 days in the placebo group (P = .002). Time to first pathologic fracture (P = .022), spinal cord compression (P = .022), need for radiation therapy to palliate bone pain (P = .054), and hypercalcemia (P = .040) were all reduced in the Zol group compared with the placebo group. The incidence of each of these events at 1 year is shown in the table . Cox regression analysis (adjusting for stratification factors) also showed that treatment with Zol significantly reduced the risk of pathologic fractures by 39% compared with placebo (hazard ratio = 0.61; P = .041). Conclusions: This prospective analysis of time to first skeletal event demonstrates that treatment of BC patients with Zol significantly delays the onset and reduces the risk of skeletal complications, including pathologic fractures, which may help preserve independence and quality of life. [Table: see text] [Table: see text]

3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases

BackgroundMetastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile.MethodsInvasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC.ResultsEnhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples.ConclusionThese results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its importance in the metastatic process.

Folate Levels and Cancer Morbidity and Mortality: Prospective Cohort Study from Busselton, Western Australia

To test a community population for the hypothesis that carcinogenesis is related to blood folate levels. Prospective analysis of cancer mortality data for a cohort of 964 men (person-time follow up: 20,254 years) and 1024 women (person-time follow up: 24,970 years) and morbidity data for a subcohort, all of whom participated in the 1969 Busselton (Western Australia) Health survey. Outcome measures were adjusted hazard ratios according to baseline folate levels for total cancer mortality and morbidity and site specific mortality and morbidity for colorectal, lung, breast, and prostate cancers. In total, there were 278 cancer deaths--45 from colorectal cancer, 44 from lung cancer, 15 from breast cancer, and 31 from prostate cancer. Decreased serum folate levels showed an independent association with increased prostate cancer mortality risk, the adjusted hazard ratio per decrease of 2 microg/L was 1.56 (CI: 1.05, 2.38), men whose levels were in the lowest quartile had an adjusted hazard ratio of 4.79 (CI: 1.56, 14.43) for subsequent death from prostate cancer. The morbidity subcohort data showed that decreased red blood-cell folate was significantly associated with increased events due to breast cancer, the adjusted hazard ratio per decrease of 100 mug/L was 1.96 (CI: 1.22, 3.12), women in the lowest quartile of red cell folate levels had an adjusted hazard ratio of 6.46 (CI: 1.19, 35.07) for a subsequent breast cancer event. Mortality and morbidity from colorectal or lung cancers were not associated with folate levels. Independent associations, assessed over periods greater than 20 years, were demonstrated between decreased folate levels and increased risks of prostate cancer mortality and breast cancer morbidity.

Méthodologie de l’enquête MISSION (Ménopause, rISque de cancer du SeIn, mOrbidité et prévaleNce)

The ambition of this article is to detail and to explain the methodology of the study named MISSION (Menopause: breast cancer risk, morbidity and prevalence). The aims of MISSION are to determine the prevalence of breast cancer and global morbidity in France among menopausal women treated or not with hormone replacement therapy (HRT) and followed by a gynecologist. 6600 menopausal women [3300 with HRT -- ie for estrogen: only estradiol via oral or transdermal administration; for progestogen: natural progesterone or assimiled or one pregnane derived (excluding medroxyprogesterone acetate) or non-pregnane derived -- and 3300 without HRT] will be enrolled in France between January 5 2004 and February 28 2005 by 825 gynecologists, members or not of the National Federation of Medical Gynecologists (FNCGM). This study design is a historico-prospective with case randomization. MISSION is conducted by a Theramex-Merck Laboratories initiative in collaboration with a WHO (World Health Organization) Collaborating Center for Public Health Aspects of Rheumatic Diseases and a multidisciplinary expert group. First results of this study will contribute to better knowledge of women health.