Classification of breast tissue density by optical transillumination spectroscopy: optical and physiological effects governing predictive value

Preventive oncology is in need of a risk assessment technique that can identify individuals at high risk for breast cancer and has the ability to monitor the efficacy of a risk reducing intervention. Optical transillumination spectroscopy (OTS) gives information about breast tissue composition and tissue density. OTS is noninvasive and in contrast to mammography, uses nonionizing radiation. It is safe and can be used frequently on younger women, potentially permitting early risk detection and thus increasing the time available for risk reduction interventions to assert their influence. Before OTS can be used as a risk assessment and/or monitoring technique, its predictive ability needs to be demonstrated and maximized through the construction of various mathematical models relating OTS and breast tissue density, and hence, risk. To establish a correlation between OTS and mammographic density principal components analysis (PCA), using risk classification, is calculated. The PCA scores are presented in three-dimensional cluster plots and a plane of differentiation that separates the high and low tissue densities is used to calculate the predictive value. Stratification of PCA for measurement position on the breast in cranial-caudal projection is introduced. Analysis of PCA scores as a function of the volunteer's age and body mass index (BMI) is examined. A small but significant correlation between the component scores and age or BMI is noted but the correlation is dependent on the tissue density category examined. Correction of the component scores for age and BMI is not recommended, since a priori knowledge of a woman's breast tissue density is required. Stratification for the center and distal measurement positions provide a predictive value for OTS above 96%.     

Computerized analysis of mammographic parenchymal patterns for breast cancer risk assessment: feature selection

Our purpose in this study was to identify computer-extracted, mammographic parenchymal patterns that are associated with breast cancer risk. We extracted 14 features from the central breast region on digitized mammograms to characterize the mammographic parenchymal patterns of women at different risk levels. Two different approaches were employed to relate these mammographic features to breast cancer risk. In one approach, the features were used to distinguish mammographic patterns seen in low-risk women from those who inherited a mutated form of the BRCA1/BRCA2 gene, which confers a very high risk of developing breast cancer. In another approach, the features were related to risk as determined from existing clinical models (Gail and Claus models), which use well-known epidemiological factors such as a woman's age, her family history of breast cancer, reproductive history, etc. Stepwise linear discriminant analysis was employed to identify features that were useful in differentiating between "low-risk" women and BRCA1/BRCA2-mutation carriers. Stepwise linear regression analysis was employed to identify useful features in predicting the risk, as estimated from the Gail and Claus models. Similar computer-extracted mammographic features were identified in the two approaches. Results show that women at high risk tend to have dense breasts and their mammographic patterns tend to be coarse and low in contrast.     

Psychological adjustment among partners of women at high risk of developing breast/ovarian cancer.

PURPOSE: The aim of the current research was to characterize psychological adjustment among partners of women at high risk of developing breast/ovarian cancer and to explore the relationship between women's and partners' adjustment. METHODS: A study of 95 unaffected at-risk women and 95 partners was carried out using mailed, self-administered questionnaires with validated measures of psychological outcome. RESULTS: Elevated levels of distress were noted in up to 10% of partners. High monitoring coping style and greater perceived breast cancer risk for their wife were associated with higher distress levels for partners. However, communicating openly with their wife and the occurrence of a recent cancer-related event in the woman's family were related to lower distress for partners. Partners' cancer-specific distress was positively related to their wives' distress. CONCLUSION: Among partners with elevated levels of distress, the ability to provide effective support to the at-risk women and participate appropriately in their decision making may be compromised. These partners are likely to benefit from targeted clinical interventions designed to reduce their distress levels. The findings emphasize the importance of considering partners of at-risk women in service provision and highlight the need for partners to obtain information and support specifically tailored to their needs.     

Inherited predisposition and breast cancer: modifiers of BRCA1/2-associated breast cancer risk

Germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes explain a substantial proportion of hereditary breast and ovarian cancer. Women who have inherited a mutation in one of these genes are at increased risk to develop breast and/or ovarian cancer, although there is variability in the manifestation of tumors by age and site. This variability may be explained, in part, by the BRCA1/2 mutation type or location. However, it is also possible that risk-modifying factors exist that explain interindividual variability in cancer risk. These factors include genes at other loci and endogenous or exogenous exposures. A more complete understanding of factors that modify cancer risk in BRCA1 and BRCA2 mutation carriers may help to refine estimates of cancer risk. A number of exposures, including reproductive history and exogenous hormone use, have been implicated as BRCA1/2-associated cancer risk modifiers. Similarly, genes involved in hormone metabolism, including the AIB1 and AR genes, have been linked with altered breast cancer risk. Therefore, although germline BRCA1/2 mutations raise a woman's breast and ovarian cancer risk, other factors may interact with BRCA1/2 mutations to modulate this risk.     

Breast cancer: hormones and other risk factors

In North America and Northern Europe, breast cancer incidence rates begin increasing in the early reproductive years and continue climbing into the late seventies, whereas rates plateau after menopause in japan and less developed countries. Female gender, age and country of birth are the strongest determinants of disease risk. Family history and mutations in the BRCA1 and BRCA2 genes are important correlates of lifetime risk. Genetic polymorphisms associated with estrogen synthesis and metabolism are currently under study. Atypical hyperplasia and molecular alterations in benign breast lesions appear to be involved in the pathogenesis of invasive carcinoma. In postmenopausal women, increased breast density on mammograms increases risk. Bone density and breast cancer are associated, presumably through the mechanism of endogenous estrogen levels. Serum estrogen levels are higher in breast cancer cases than controls. Many established risk factors for breast cancer may function through and endocrine mechanism. Current use of oral contraceptives and prolonged, current or recent use of hormone replacement therapy moderately increase risk. Tamoxifen and possibly other selective estrogen receptor modulators reduce breast cancer risk in high risk women. Relationships between various dietary micro and macronutrients and breast cancer have been suggested but require evaluation in clinical trials. Whereas alcohol consumption is associated with increased risk, most environmental factors, including polychlorinated compounds and electromagnetic fields, are not. Conclusion: Breast cancer etiology is becoming clearer through the study of molecular alterations in germline and somatic cell genes, and the interaction of these genes with steroid hormones and relevant growth factors. This knowledge should be useful for breast cancer prevention.     

The credibility of the Breast Cancer Risk Assessment (BCRA) tool for Asians

This paper presents an overview of the Breast Cancer Risk Assessment (BCRA) Tool, assessing the credibility of the BCRA tool in estimating the risk of developing breast cancer for Asians and the carrying out of tests to identify the changes in the risks that follow with changes in one or more risk factors of the tool. It is essential to increase the awareness of women of their risk of developing breast cancer, as it is not surprising that some women may not even be conscious of the individual factors that might contribute to the increase of their risk of developing breast cancer. On the other hand, relatively accurate means of determining increases in relative risks of developing breast cancer due to changes in some of the risk factors are also important. This is done so that unnecessary worry due to an overestimation of an individual's risk of developing breast cancer can be avoided. Due to the origin of the BCRA tool which is used in this study, it is important to verify the validity of the tool on Asians and to identify, as far as possible, the effect that each risk factor has on individuals. The effect that a specific risk factor has on a white woman may not be exactly the same for that of an Asian woman. As the above-mentioned tool has been arrived at using the statistics and databases of white women, in this work, tests have been carried out to determine the suitability of the tool on Asian women. On top of that, various tests are also carried out to determine the effects of the change of certain risk factors on a woman's risk of developing breast cancer. These factors include age, number of breast biopsies and number of first-degree relatives with breast cancer. Five-year risks and lifetime risks are also looked into separately with the change of each of these factors.     

Justification for the use of HRT in the long-term prevention of osteoporosis

Osteoporosis is a common condition in postmenopausal women and is associated with significant healthcare costs, morbidity and mortality. It is clear that long-term hormone replacement therapy (HRT) has a role to play in preventing osteoporosis by increasing bone mineral density and reducing fracture rate. It is important that these benefits, as well as those on climacteric symptoms, quality of life, colorectal carcinoma and cognition, are not underestimated in the face of the postulated risks with regard to breast cancer and cardiovascular disease. In conclusion, HRT should currently be used only for women with climacteric symptoms or an increased risk of osteoporosis, and it is important that there is an individualised approach to treatment based on each woman's risk profile.     

Hormones and breast cancer

The incidence of breast cancer in women varies with age, mammarygland mass and exposure to endogenous and exogenous hormones.Age is the single most important factor and if, as projected,32% of women will be aged >60 years by 2050, world breast cancerincidence will exceed the current 10⁶ per year. Hormonal influencesthat affect growth of the mammary gland increase the risk ofbreast cancer; for example earlier menarche and later menopause.Childbearing protects against later development of breast cancer,and breastfeeding further decreases the risk. The breast cancerrisk declines more with increasing total duration of breastfeeding.Exposure to hormonal contraceptives has been evaluated in acombined reanalysis of data from 51 epidemiological studies.There is a small transient increase in the relative risk ofbreast cancer among users of oral contraceptives but, sinceuse typically occurs at young ages when breast cancer is relativelyrare, such an increase would have little effect on overall incidencerates. In contrast, exposure to menopause hormone treatmentoccurs when the baseline risk of breast cancer is higher, andepidemiological studies and randomized controlled trials consistentlyfind an increase in breast cancer risk with exposure to combinedestrogen and progestogen. Women with a family history of breastcancer in first degree relatives have an increased risk of breastcancer but there is no evidence to suggest that this differsaccording to a woman's use of oral contraceptives or menopausehormone treatment. Selective estrogen receptor modulators areuseful in the treatment and/or prevention of breast cancer dependingon the specific agonist or antagonist effects on estrogen targettissues.     

How making a risk estimate can change the feel of that risk: shifting attitudes toward breast cancer risk in a general public survey

Counseling women about breast cancer risks has been found to decrease screening compliance. We investigated whether women's reactions to risk information are an artifact of requiring women to estimate the risk of breast cancer prior to receiving risk information. Three hundred and fifty-six women were randomized to either make or not make a risk estimate prior to receiving risk information. Outcome measures were participants' estimates of the average woman's breast cancer risk and their emotional response to the risk information. Women overestimated the lifetime risk of breast cancer (M = 46%). Women who made risk estimates felt more relieved about the risk and perceived the risk as being lower than women who did not make estimates (p's < 0.001). Asking people to estimate risks influenced their subsequent perceptions of the risk of breast cancer.     

Prolactin does not cause breast cancer and may prevent it or be therapeutic in some conditions

The polypeptide hormone prolactin (PRL), ubiquitous and multifunctional in vertebrates, always interested biologists, was of restricted concern to clinicians and researched little compared to insulin and growth hormone. PRL in lactation initially aroused relatively little interest, but it rose when with ovarian steroids and chemical carcinogens, it was implicated in rodent mammary carcinoma. It declined when PRL suppression did not counter breast cancer. Meanwhile, long-known, estrogen-related cancers in the ovary and breast did not deter wide estrogen use for contraception and supplementation despite risk, and estrogen blockers and inhibitors have improved treatment and are on trial for prophylaxis, despite serious short and long term side-effects. Despite the great differences between steroid and polypeptide, research on PRL and breast cancer mirroring that on estrogens is now growing. This is mainly negative, much due to recent prospective research reporting minor rises in plasma levels as a basis, together with some recent laboratory research, for a hypothesis that PRL induces post-menopausal breast cancer. That view contradicts a reproductive biology that evolved to benefit women and offspring. Elevated PRL in pregnancy and probably that in lactation, reduce risk. Many exogenous chemical and physical PRL-stimulants also do not increase risk. It has not been shown that PRL increases risk of breast cancer and some older and recent cell and tissue data suggest it may be the key, two-sided, in human breast tissue homeostasis. Excessive disturbance of this is unlikely to originate in PRL itself. The natural biology of PRL, the reproductive woman's hormone par excellence, and research in various fields, suggest a positive potential in the PRL family for direct prevention and treatment of breast cancer, possibly greater than that in the estrogens. It is time to debate and research this.     

X-光照片上的乳腺组织结构特征和乳腺癌发生率的关系

从美国的很多研究结果显示：美国妇女的乳腺癌发病率和很多因素有关，这些因素包括妇女的年龄，乳腺癌的家史，个人乳腺癌病史，个人乳腺良性增生病史，以及第一次来月经的时间以及生产的年龄，同时研究还显示，反应在乳腺影像上的乳腺组织密度增加也会提高乳腺癌发病率的增长，本文使用计算机图像识别的方法;研究乳腺组织结构，找出与乳腺癌发病率有关的X－光照片上影像的特征并用这些特征预测乳腺癌发病的几率。     

Noninvasive assessment of breast cancer risk using time-resolved diffuse optical spectroscopy

Breast density is a recognized strong and independent risk factor for breast cancer. We propose the use of time-resolved transmittance spectroscopy to estimate breast tissue density and potentially provide even more direct information on breast cancer risk. Time-resolved optical mammography at seven wavelengths (635 to 1060 nm) is performed on 49 subjects. Average information on breast tissue of each subject is obtained on oxy- and deoxyhemoglobin, water, lipids, and collagen content, as well as scattering amplitude and power. All parameters, except for blood volume and oxygenation, correlate with mammographic breast density, even if not to the same extent. A synthetic optical index proves to be quite effective in separating different breast density categories. Finally, the estimate of collagen content as a more direct means for the assessment of breast cancer risk is discussed.     

Screening for osteoporosis after breast cancer: For whom,why and when

Osteoporosis and breast cancer are common diseases in postmenopausal women. Bone and the breast are both estrogenic dependent tissues and different surrogate markers for osteoporosis are opposite of those for the risk of breast cancer. In particular, numerous studies have reported a positive relationship between high bone mineral density (BMD) and a greater risk of breast cancer. On the other hand, most treatments in early breast cancer women including ovarian suppression treatments (chemotherapy, surgery or GnRH agonists) and aromatase inhibitor (AI) therapy induce a profound and rapid suppression of estrogen levels thereby increasing the rate of bone loss. Nevertheless, their impact on the risk of fracture is still questionable, especially in postmenopausal women with no osteoporosis at baseline. The purpose of this minireview is to examine the relationship between breast cancer and the risk of fracture and to discuss a screening strategy for osteoporosis after breast cancer.     

Postmenopausal hormone therapy and the risk of breast cancer: the view of an epidemiologist

OBJECTIVES: Postmenopausal hormone therapy (PMH) has been widely used by menopausal women living in western countries for the past several decades. Numerous studies have evaluated the relationship between PMH and breast cancer risk because steroid hormones have been implicated in breast cancer etiology. METHODS: A review of selected studies was performed to evaluate the history of investigations of the association between PMH and breast cancer, with a focus on studies evaluating different PMH regimens and different histologic types of breast cancer. RESULTS: Though studies conducted before the early 1990s suggest that both combined estrogen and progestin (E + P) PMH and unopposed estrogen (E) PMH are associated with an increased risk of breast cancer, more recent observational studies suggest that E + P, particularly current use for 5 years or longer, is more strongly associated with breast cancer risk than is unopposed E. Results from the Women's Health Initiative (WHI) randomized trials have confirmed these findings as they indicate that E + P is causally related to breast cancer (relative risk (RR) = 1.24; 95% confidence interval (CI): 1.01-1.54), while E alone is not (RR = 0.77; 95% CI: 0.59-1.01). CONCLUSIONS: There is clear and consistent evidence that use of E + P increases a woman's risk of breast cancer. Alternatively, current evidence suggests that use of unopposed E is not as strongly associated with breast cancer risk. Further studies are needed though to examine how different PMH regimens, doses, and methods of delivery are related to breast cancer risk, and how PMH impacts the risks of different types of breast cancer.     

Population-based screening for hereditary breast cancer in a region of North-Central Italy

Assessment of family history is an important element in the identification of individuals and families likely to be at risk of hereditary cancers. It is based on the recognition of important features in the natural history of cancer syndromes. These include the occurrence of the same type of cancer in two or more close relatives, bilateral cancer in paired organs, multiple primaries in the same individual, early age at onset, a specific constellation of cancers or other physical findings associated with a known syndrome, and a mendelian pattern of inheritance. We set up a population-based screening program to identify women at increased risk of breast or ovarian cancer in a region of North-Central Italy. As a preliminary screening, 159 women with a family history of breast and ovarian cancer were recruited at the Cancer Prevention Unit of Pierantoni Hospital in Forli. Information on the number of affected individuals and the age at onset of breast or ovarian cancer in each woman's family was recorded. Thirty-nine women reported two or more first- or second-degree relatives with breast cancer under the age of 50 (25%) and 95 a single first- or second-degree relative with breast cancer under the age of 50 (60%) with or without other late onset breast cancers in the family. The remaining 25 women reported first- and second-degree relatives with breast cancer over the age of 50 (15%). There were five families with a history of ovarian cancer (3%), one of which comprised 3 affected members. Twenty-three families showed multiple cancers associated with breast cancer cases. Associated prostate and colorectal cancers were found in 5 and 4 families with a history of breast cancer, respectively. On the basis of these preliminary data, we aimed to extend the population-based screening to the whole of the Emilia-Romagna population, involving the Cancer Prevention Units of neighboring towns and adopting homogeneous family history evaluation and risk assessment criteria.     

Prophylaxis approach to a-symptomatic post-menopausal women: breast cancer

Breast cancer is the most common cancer of women worldwide. Its frequency increases throughout the female lifespan. Epidemiological research has clearly identified important reproductive risk factors for breast cancer, including age at menarche, age at menopause, age at first-term pregnancy and nulliparity, which provide important clues to the hormonal origin of this disease. The widespread use of exogenous sex steroids as contraceptive agents and as hormonal replacement therapy has been a source of concern and generates discussion about their effects on breast health. Lifestyle changes, exercise or diet could play a role in primary prevention of breast cancer. Regular exercise, ingestion of adequate amounts of fruit and vegetables, limiting alcohol consumption, avoidance of obesity in post-menopausal women, and perhaps the use of olive oil, may all have a protective effect and should be considered by women. There is insufficient scientific evidence of the role played by phyto-oestrogens on breast cancer risk. Other preventive measures that include the use of drugs such as statins or aspirin should not be recommended until we have more information about their effects on the breast. Especially for high-risk women, all the aforementioned measures may be not enough, and chemo-prevention should be considered. The use of selective oestrogen receptor modulators (SERMs) to reduce breast cancer risk is still being evaluated. Tamoxifen was the first SERM approved for the reduction of breast cancer incidence in women at high risk. However its use has limitations, due to significant side effects. Raloxifene has been approved for the prevention and treatment of post-menopausal osteoporosis and has provided excellent indications of breast cancer risk reduction, with a more favourable profile than tamoxifen.     

Postmenopausal hormone therapy before and after breast cancer: clinical experiences

Conventional oestrogen-based hormone therapy (HT) increases the incidence of breast pain and tenderness, mammographic density and the risk of breast cancer. Combined oestrogen plus progestogen therapy (EPT) increases the risk of breast cancer to a greater degree than oestrogen alone (ET). Attention must therefore be focused on identifying women at risk of breast cancer or on producing a HT that has fewer breast side effects. Randomised controlled trials have shown that while EPT induces breast tenderness or pain in up to 50% of women and increases mammographic density in up to 70% during the first year of treatment, only about as many as one-tenth women report breast tenderness or pain with tibolone and increases in mammographic density are rare, occurring with a similar incidence as seen in untreated controls. Many women with breast cancer suffer vasomotor symptoms rather than risk recurrence with conventional HT. However, in a small randomised controlled trial in women with early breast cancer undergoing adjuvant tamoxifen treatment, tibolone reduced hot flushes, night sweats and improved quality of life compared with placebo.     

Breast cancer patients' experiences of patient-doctor communication: a working relationship

The traumas of diagnosis and treatment for breast cancer are well researched and generally addressed in care. While women with breast cancer continue to identify the need for better communication with physicians, studies to date have not investigated how the process of communication between physicians and women with breast cancer actually unfolds. This phenomenological study therefore explored how women with breast cancer experience patient-physician communication to gain a greater understanding of effective approaches. Interviews of a purposeful sample of 11 women within 6 months of initial diagnosis or recurrence of breast cancer were audiotaped, transcribed verbatim and analyzed using inductive interpretation. Themes and patterns of positive and negative experiences emerged. All experiences began with the woman's feeling of vulnerability. In positive experiences, information sharing and relationship building were inextricably linked components of a working relationship which was at the same time affective, behavioural and instrumental. This experience, in turn, influenced the woman's experience of control and mastery of the illness experience, and their experience of learning to live with breast cancer. Findings illuminate the importance of comprehensively patient-centred, working relationships. Several specific techniques to enhance effective communication are identified.     

The risk of breast cancer after irradiation of the thymus in infancy

It is well established that exposure to ionizing radiation during or after puberty increases a woman's risk for breast cancer, but it is less clear whether exposure to ionizing radiation very early in life is also carcinogenic. We studied the incidence of breast cancer prospectively in a cohort of 1201 women who received x-ray treatment in infancy for an enlarged thymus gland and in their 2469 nonirradiated sisters. After an average of 36 years of follow-up, there were 22 breast cancers in the irradiated group and 12 among their sisters, yielding an adjusted rate ratio of 3.6 (95 percent confidence interval, 1.8 to 7.3). The estimated mean absorbed dose of radiation to the breast was 0.69 Gy. The first breast cancer was diagnosed 28 years after irradiation. The dose-response relation was linear (P less than 0.0001), with a relative risk of 3.48 for 1 Gy of radiation (95 percent confidence interval, 2.1 to 6.2) and an additive excess risk of 5.7 per 10(4) person-years per gray (95 percent confidence interval, 2.9 to 9.5). We conclude that exposure of the female breast to ionizing radiation in infancy increases the risk of breast cancer later in life.