A follow-up study of 105 women with breast cancer following reduction mammaplasty.

Reduction mammaplasty is one of the most common procedures performed by plastic surgeons in Canada. In a recent study of 27,500 women in the province of Ontario who underwent breast reduction surgery, 105 women were identified who developed breast cancer after reduction mammaplasty. The purpose of this study was to compare women who had breast cancer and had a previous breast reduction with women who had breast cancer but did not have a breast reduction. Specifically, we wanted to document patient demographics, cancer type, surgical and nonsurgical treatment, and eventual outcome. A comparison group of non-breast reduction women was taken from the cohort of breast cancer patients in the province of Ontario, and the two groups were matched for age, year of diagnosis, and place of diagnosis. It was found that (1) the average age at diagnosis of breast cancer is significantly younger for women who have had previous breast reduction surgery than for those who have not; (2) the median interval between breast reduction and cancer is 5 years; (3) the type, location, and side of breast cancers are similar in the two groups of women; (4) breast reduction does not significantly increase or decrease survival rate from breast cancer; and (5) women who have had breast reduction receive the same treatment for their breast cancer as women who have not had reduction mammaplasty.     

Approaches to improving breast cancer diagnosis using a high resolution,breast specific gamma camera

Mammography remains the gold standard in breast cancer detection, although there remains a challenge for improvement in sensitivity of breast cancer detection and diagnosis. Although mammography is the most frequently utilized examination to screen for breast cancer, which has resulted in a reduction of breast cancer mortality, still some cancers are unable to be visualized on mammographic images. Mammography films are interpreted using an anatomic approach. A new approach to breast cancer diagnosis utilizes a breast specific gamma camera to measure radiotracer uptake of abnormal tissue in the breast in patients with an abnormal mammogram or palpble mass using technetium sestamibi. Images are taken using the same positioning techniques as mammography for comparison of both types of images. Multi-Institutional trials using a traditional gamma camera demonstrated potential for this approach. However, the inability of traditional gamma camera intrinsic resolution and non-optinuized breast imaging limited scintimammography. Therefore, a breast specific, high resolution gamma camera was developed to overcome these limitations.Results of clinical studies evaluating BSGI are promising and are increasingly being used. Additionally, means for minimally invasive imaging-guided acquisition of tissue are being developed so that biopsies will be avaibles for areas of interest based on radiotracer uptake.Breast specific gamma camera nuclear imaging of the breast is a developing and increasingly utilized approach to improving breast cancer detection and diagnosis.     

Breast cancer gene discovery

Many important advances have been made in the past decade in understanding breast cancer at the molecular level, and two important high-penetrance breast cancer genes--BRCA1 and BRCA2--have been identified. However, germline mutations in these two genes are responsible for only a minority (approximately 5%) of all breast carcinomas, and the genes responsible for the majority of breast cancer cases remain to be identified. There is evidence that there are additional high-to-moderate-penetrance breast cancer susceptibility genes but, given the high degree of molecular heterogeneity in breast carcinomas, it is likely that each of these genes is responsible for only a subset of cases. There are also many candidate low-penetrance breast cancer genes and many more are likely to be identified. In addition to germline, and somatic, sequence alterations, epigenetic changes in many genes are likely to play an important role in the pathobiology of breast cancer. Recently developed genomic technologies and the completion of the human genome sequence provide us with powerful tools to identify novel candidate breast cancer genes that could play an important role in breast tumourigenesis.     

Breast cancer 2004: Progress and promise on the clinical front

Carcinoma of the breast is the most common cancer in u.s. women (excluding skin cancer), and the second leading cause of cancer-related mortality. In 2004, it is estimated that 215,000 u.s. women will develop invasive breast cancer, and 40,000 women will die of the disease. Advancing age and female sex are the two greatest risk factors for the development of breast cancer, although family history, reproductive and hormonal history, lifestyle and environmental factors all contribute to risk. Models are available to help estimate risk of developing breast cancer in individual patients. Inherited mutations, specifically in the genes BRCA1 and BRCA2, account for approximately 5–10% of all breast cancer cases. Significant advances have recently been made in both the primary prevention of breast cancer (including chemoprevention), and secondary prevention (early detection through breast imaging). Breast mri as a tool for screening high risk women is a particularly exciting new tool.When breast cancer is diagnosed, optimal treatment involves a multidisciplinary approach, including surgery, radiation therapy, and systemic therapies. In the field of breast surgery, breast conservation and sentinel lymph node biopsy techniques have allowed substantially decreased surgery in appropriated selected patients with corresponding decreases in complication rates and long-term sequelae. Radiation oncologists are comparing partial breast irradiation versus conventional whole breast radiation in an attempt to minimize toxicity and treatment time, and maximize efficacy. The field of breast medical oncology has evolved at a rapid pace in the past decade, with numerous new hormonal agents, chemotherapeutic agents, and biologically targeted therapies in clinical use and under investigation. The addition of ‘adjuvant’ systemic therapy to the treatment of early stage breast cancer patients has dramatically reduced relapse and death rates. Unfortunately, metastatic recurrence still occurs. Once the cancer has spread beyond the breast and locoregional nodal areas it is felt to be incurable, although still treatable. A better understanding of breast cancer biology has led to the development of a host of new biologically targeted agents, many of which hold substantial promise for improving quality of life and survival rates in metastatic breast cancer patients.     

A review of psychological outcomes and suicide in aesthetic breast augmentation

Aesthetic surgery is an essential component of plastic surgery and has become increasingly popular in American society. In 2002, 1.8 million surgical cosmetic procedures were performed in the United States, representing a 294 percent increase from 1992. The 1992 U.S. Food and Drug Administration moratorium on silicone breast implants arose in response to numerous reports of connective tissue disease associated with silicone gel breast augmentation and has led to a decade-long battle over the safety of silicone breast implants that continues today. Numerous scientific and epidemiologic studies of the past decade have established that there is no association between silicone breast prostheses and systemic disease. Recently, a new front has opened in the conflict regarding the safety of breast augmentation: the psychological impact of breast augmentation. Quality studies assessing the psychological characteristics of breast augmentation patients and the psychological impact of breast augmentation surgery are few and most studies are flawed in their methods. Recent reports have provided corroborating evidence to support the psychological benefits of cosmetic surgery and breast augmentation. New reports citing an increased risk for suicide among women with breast implants have brought renewed concerns but are unable to demonstrate a cause-and-effect relationship between breast implants and suicide. The present challenge is to determine whether the increased risk reported in epidemiologic studies is falsely associated with breast implants or whether it represents underlying risk factors or psychopathology in women undergoing breast augmentation that puts them at increased risk for suicide. The purpose of this article is to review the literature regarding the psychological impact of breast augmentation and assesses current scientific findings, with emphasis on the validity of suicide risk in breast augmentation patients.     

An overview of the research progress of BRCA gene mutations in breast cancer

The breast cancer susceptibility gene (BRCA) is an important tumor suppressor gene, including BRCA1 and BRCA2, a biomarker that assesses the risk of breast cancer and influences a patient's individualized treatment options. BRCA1/2 mutation (BRCAm) increases the risk of breast cancer. However, breast-conserving surgery is still an option for BRCAm, and prophylactic mastectomy and nipple-sparing mastectomy may also reduce the risk of breast cancer. BRCAm is sensitive to Poly (ADP-ribose) polymerase inhibitor (PARPi) therapy due to specific types of DNA repair defects, and its combination with other DNA damage pathway inhibitors and endocrine therapy and immunotherapy are also used for the treatment of BRCAm breast cancer. The current treatment and research progress of BRCA1/2 mutant breast cancer in this review provides a basis for the individualized treatment of patients with this type of breast cancer.     

Breast cancer stage at diagnosis and survival among patients with prior breast implants

Longstanding concern exists regarding the potential for women with breast implants to experience delayed detection of breast cancer. Furthermore, survival among cosmetic breast implant patients who subsequently develop breast cancer is a concern. Since 1976, this institution has monitored cancer incidence in a cohort of 3182 women who underwent cosmetic breast augmentation between 1959 and 1981. The distributions of stage at diagnosis and survival of the 37 women who subsequently developed in situ or invasive breast cancer were compared with the observed population distributions. The distribution of stage at diagnosis for cosmetic breast implant patients who subsequently developed breast cancer was virtually identical to that of all breast cancer patients in Los Angeles County who were of the same age and race, and were diagnosed during the same time period. Furthermore, the 5-year survival rate of the 37 patients did not differ from that which would be expected based on rates established by the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. These results suggest that cosmetic breast implant patients are not at increased risk of delayed detection of breast cancer, nor do they suffer a poorer prognosis when breast cancer does occur. Although the number of breast cancer patients in this study is small, the results are highly consistent with the existing epidemiologic evidence related to breast cancer detection and survival among breast implant patients. Although breast implant patients should continue appropriate breast cancer screening behavior, there seems to be no cause for alarm.     

Breast reduction surgery and breast cancer risk: does reduction mammaplasty have a role in primary prevention strategies for women at high risk of breast cancer?

Prophylactic bilateral mastectomy has been demonstrated to reduce breast cancer incidence in women with a high inherited susceptibility to breast cancer. For the majority of high-risk women, however, bilateral prophylactic mastectomy is not an acceptable option for primary prevention of breast cancer. Several epidemiological follow-up studies have indicated that there may be a substantial reduction in breast cancer risk among women who have undergone breast reduction surgery. The authors reviewed the evidence from these studies, with emphasis on the problems inherent in interpreting the results of nonexperimental studies of elective medical procedures. Although such observational studies cannot demonstrate definitively that reduction mammaplasty reduces the risk of breast cancer, the evidence from these studies is sufficiently strong to warrant the evaluation of breast reduction surgery as an option for primary prevention in clinical studies of women at increased risk of breast cancer. The availability of a more acceptable surgical option for primary prevention of breast cancer could increase the number of women willing to choose risk reduction surgery and thus may result in an overall reduction in breast cancer mortality among high-risk women.     

Integrated breast mound reduction and nipple reconstruction with the wraparound flap.

A new method for nipple reconstruction is described that combines revision of an autologous tissue breast mound with creation of a projecting nipple. The method is applicable only to reconstructed breast mounds that must be reduced or lifted to achieve symmetry with the opposite breast. In this technique, the mound is reduced as if it were a normal breast, using an inverted-T or vertical mammaplasty pattern. In this way, breast projection can be increased and, if necessary, the inframammary fold can be elevated. A rectangular flap is created from skin and subcutaneous tissue that would normally be discarded during the breast reduction, and this flap is wrapped around on itself to form a projecting nipple. This new technique avoids the flattening of the breast mound usually seen after nipple reconstruction because it does not take tissue away from the completed breast mound to make the nipple. In appropriate patients who require reduction in size of their reconstructed breast mound, the wraparound flap nipple reconstruction is worth considering.     

Risk factors and risk reduction of breast cancer

Because of its increasing incidence, breast cancer is a significant burden for women worldwide. In industrialized countries, breast cancer is the second-leading cause of cancer-related deaths among women, and it is estimated that 1 in every 8 women will develop the disease during her lifetime. Sufficient evidence indicates that a number of genetic, environmental and lifestyle risk exposures during life may play important roles in the etiology of this disease. The purpose of this paper is to review some etiologic factors and underlying mechanisms in relation to breast cancer risk. Based on the published literature, there is sufficient evidence that some established factors are associated with breast cancer risk. Age, early age at menarche, late menopause, height, post-menopausal obesity, family history of breast cancer, ionizing radiation, oral contraceptives, hormonal replacement therapy, mammographic density, some gene mutations and clinical conditions, such as benign breast disease, are associated with an increased risk of breast cancer. The risk decreases with early childbearing, high parity and physical activity, and breastfeeding. Alcohol increases the risk, while caloric restriction may confer protection from breast cancer. Epidemiological evidence for other nutritional factors is insufficient. These results suggest that breast cancer is a multifactorial disease where genetic susceptibility, environment, nutrition and other lifestyle risk factors interact. Better identification of modifiable risk factors and risk reduction of breast cancer may allow implementation of useful strategies for prevention.     

Estrogen receptor beta in breast cancer—Diagnostic and therapeutic implications

More than 10 years have passed since the discovery of the second estrogen receptor, estrogen receptor β (ERβ). It is now evident that ERα is not the only ER in breast cancer cells; in fact, ERβ is expressed in the majority of breast cancers although at lower levels than in the normal breast. In addition, ERβ is expressed in breast cancer infiltrating lymphocytes, fibroblasts and endothelial cells, all known to influence tumor growth. By overexpressing or knocking-out ERβ in breast cancer cell lines, several researchers have investigated its function with respect to proliferation and tumor growth. It appears that ERβ is anti-proliferative, in many ways antagonising the function of ERα. Furthermore, phytoestrogens have a binding-preference for ERβ and several epidemiological studies indicate a breast cancer preventing effect of this class of compounds. Tamoxifen is one of the standard, adjuvant treatments for ERα positive breast cancer, classically thought to mediate its effect through ERα. However, in several recent studies, ERβ has been described as a potential marker for tamoxifen response. In summary, experimental, epidemiological as well as diagnostic studies point towards ERβ as an important factor in breast cancer, opening up the possibility for novel ERβ-selective therapies in the treatment of breast cancer.     

Chemoprevention of breast cancer - with special interest of tamoxifen

The adjuvant use of tamoxifen confers a survival advantage for patients with node-positive and node-negative breast cancer and demonstrated benefit when used alone or in combination with chemotherapy to treat advanced breast cancer.Tamoxifen prevents induced mammary cancer in rats, decreases the contralateral breast cancer incidence in humans, and its safety record in clinical practice is excellent. This finding led to the concept that the drug might play role in breast cancer prevention. In 1986 at the Royal Marsden Hospital a small pilot study was started, which would serve as a feasibility assessment for a larger trial to determine if tamoxifen prevents breast cancer. The trial shows no effect, because the study is too small for accurate results. Similarly, in another tamoxifen prevention study performed in Italy, the incidence of breast cancer did not differ between groups of tamoxifen and placebo. The negative finding of the study is readily explained by the relatively low risk of breast cancer development in the study population, the high drop-out rate and the small number of women who completed 5 years of treatment. In the NSABP P-1 prevention trial tamoxifen reduced the risk of invasive breast cancer by 49% and of noninvasive breast cancer by 50% in the increased risk population of 13.388 healthy women. The article summarizes the recent theoretical and practical data of the chemoprevention of breast cancer.     

Refinements in transverse rectus abdominis myocutaneous flap breast reconstruction: projection and contour improvements

A surgical procedure with the transverse rectus abdominis myocutaneous (TRAM) flap for breast reconstruction is presented using parameters from the opposite normal breast to achieve a better cone shape in the new breast to project the nipple-areola complex. This cone projection is obtained through a vertical plication of both skin/fat halves of the TRAM flap and with two supraumbilical fat flaps to avoid cone collapse. The infraclavicular and axillary regions are filled with a de-epithelialized "fish-fin" cutaneous-fat or fat-only flap, which is placed as a lateral TRAM extension. The de-epithelialized lateral extremity of the TRAM flap folded over itself gives a mound shape to the lateral aspect of the new breast, and the inverted umbilical stalk attached to the TRAM flap imitates a nipple. This procedure is based on six breast reconstructions with a 2-year follow-up. The procedure is a simple, safe, and versatile way to mimic the opposite breast. It is mostly indicated for thin patients who have small to moderate breasts without ptosis or hypertrophy who refuse breast implants or request a mastopexy or reduction mammaplasty on the opposite normal breast during the same procedure.     

Expression of genes coding for pS2, c-erbB2, estrogen receptor and the H23 breast tumor-associated antigen. A comparative analysis in breast cancer

Expression of the gene coding for a new breast tumor-associated antigen, H23, was compared to expression of genes coding for pS2, c-erbB2 and estrogen receptor (ER). Comparison involved mRNA expression in normal and malignant breast tissues as well as in non-breast tumors. Results obtained by RNA dot blot and Northern hybridizations showed that expression of the H23 antigen coding gene is a discriminatory marker in human breast cancer. It is expressed in 92% of breast tumors whereas 69%, 62% and 56% of breast tumors demonstrate significant mRNA levels of c-erbB2, ER and pS2, respectively. Non-malignant or normal breast tissue expresses much lower levels of the H23 antigen mRNA. From the comparative analysis presented here it is concluded that the gene coding for H23 antigen furnishes a most useful marker for human breast cancer.     

Raman 'optical biopsy' of human breast cancer

Raman imaging (RI) is a novel method of medical diagnostics of human breast cancer and has a potential to become a routine optical biopsy. Up to date the present study is the most statistically reliable Raman analysis based on data of normal, benign, and cancerous breast tissues for 146 patients. This paper present the first Raman 'optical biopsy' images of the normal and cancerous breast tissue of the same patient. The results presented here demonstrate the ability of Raman spectroscopy to accurately characterize cancer tissue and distinguish between normal (noncancerous), and cancerous types. The results provide evidence that carotenoids and lipids composition of cancerous breast tissues differs significantly from that of the surrounding noncancerous breast tissue and may be a key factor responsible for mechanisms of carcinogenesis. We have found that fatty acid composition of the cancerous breast tissue is markedly different from that of the surrounding noncancerous breast tissue. The cancerous breast tissue seems to be dominated by the metabolism products of the arachidonic acid - derived cyclic eicosanoids catalyzed by cyclooxygenase, while the noncancerous breast tissue is dominated by monounsaturated oleic acid and its derivatives.     

Development of novel steroid sulfatase inhibitors; II. TZS-8478 potently inhibits the growth of breast tumors in postmenopausal breast cancer model rats

In postmenopausal breast cancer tissue, steroid sulfatase (STS) activity is high and much estrone sulfate also exists; these facts reveal that estrone sulfate may be involved in the growth of breast cancer as an estrogen source. Steroid sulfatase is an enzyme, which catalyzes hydrolysis from estrone sulfate to estrone, and the development of steroid sulfatase inhibitors is expected as novel therapeutic drugs for postmenopausal breast cancer. We have developed a novel compound 2',4'-dicyanobiphenyl-4-O-sulfamate (TZS-8478), which has potent steroid sulfatase-inhibitory activity and exhibits no estrogenicity in vitro and in vivo. To elucidate its usefulness as a therapeutic drug for postmenopausal breast cancer, we examined the breast cancer cell proliferation- and breast tumor growth-inhibitory activity of TZS-8478 in postmenopausal breast cancer model rats. TZS-8478 dose-dependently suppressed the estrone sulfate-stimulated proliferation of MCF-7 cells. Regarding nitrosomethylurea (NMU)-induced postmenopausal breast cancer models, furthermore, TZS-8478 (0.5 mg/kg per day) markedly inhibited the estrone sulfate-stimulated growth of breast tumors similarly to estrone sulfate-depletion. TZS-8478 completely inhibited steroid sulfatase activity in tumor, uterus and liver, and also markedly lowered plasma concentrations of estrone and estradiol. The above mentioned results suggested that TZS-8478 may be useful as a therapeutic drug for estrogen-dependent postmenopausal breast cancer.     

A cohort study of breast cancer risk in breast reduction patients.

Surgical reduction of the female breast (reduction mammaplasty) is very common in plastic surgery. The purpose of this study was to determine whether women who have undergone breast reduction surgery are at the same, greater, or lesser risk of developing breast cancer than women who have not undergone breast reduction surgery. This study incorporates a population-based, non-concurrent cohort linkage methodology. The Canadian Institute for Health Information hospital records were used to identify all Ontario women who had undergone breast reduction surgery in Ontario between 1979 and 1992. Three computerized probabilistic record linkages were performed. The first linkage was between a file of the 28,042 Ontario women who had undergone bilateral breast reduction surgery between April 1, 1979, and December 31, 1992, and a file of incident cancer cases among Ontario women for the calendar period 1979 to 1993. Follow-up of the cohort was undertaken starting from the date of breast reduction surgery, and vital status was ascertained as of December 31, 1993, by record linkage with the Ontario Mortality Database maintained at the Ontario Cancer Registry. The incidence of cancer in the Ontario breast reduction cohort was compared with the cancer incidence of the general Ontario population after appropriate adjustments for age and calendar time period. The expected number of cancers was calculated using the "PERSON YEARS" computer program. Within the cohort, followed for an average of 6.5 years after bilateral breast reduction surgery, 101 breast cancers were observed and 165.8 were expected, for a standardized incidence ratio of 0.61 (0.50 to 0.74, 95 percent confidence interval). This effect was independent of patient age at breast reduction. This study demonstrates that there is no increased risk of breast cancer after bilateral breast reduction surgery and, in fact, a significant decreased risk existed in women followed for an average of 6.5 years.