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Expression of BCL-2 in primary breast cancer and its correlation with tumour phenotype. For the International (Ludwig) Breast Cancer Study Group.

BACKGROUND: The role of apoptosis (programmed cell death) in the development and progression of breast cancer is unknown. Recently the bcl-2 gene has been shown to block apoptosis and thus may promote tumour development. BCL-2 is localized to the luminal cells of the normal breast, which are considered to be the origin of malignant breast disease. PATIENTS AND METHODS: Immunocytochemistry using anti bcl-2- antibody was performed on 107 breast cancer specimens belonging to node-positive patients from the Ludwig Breast Cancer Studies I-IV and the results were correlated with survival, tumour grade, S-phase, oestrogen and progesterone receptor status and c-erb B-2 expression. Western and Southern blotting together with immunofluorescence were performed on the breast cancer cell lines BT-20, BT-474, MDA-MB-361, T47-D and MCF-7. RESULTS: In the breast cancer derived cell line MCF-7 BCL-2 is expressed to a level similar to that of the B-lymphoma cell line Karpas 231 with t(14;18)(q32.3;q21.3), but no evidence of a rearrangement or gene amplification was identified. In a study of 107 breast cancers from the International Breast Cancer Study Group Trials I-IV we have demonstrated a very significant inverse correlation of BCL-2 with c-erbB-2 expression (p = 0.002), and a positive correlation with oestrogen receptors (p = 0.001) and progesterone receptors (p = 0.05). In this study there was no correlation of expression with S-phase fraction in the tumours or with any stage in the cell cycle as assessed in MCF-7 cells. CONCLUSION: We conclude that BCL-2 might contribute to the malignant phenotype of breast cancer by modulation of biological behaviour of cancer cells.

Adult↗

Can breast reconstruction with gel-filled silicone implants increase the risk of death and second primary cancer in patients treated by mastectomy for breast cancer?

An increased risk of cancer and autoimmune disease associated with gel-filled silicone implants has been suggested recently, but these possible detrimental effects have not been adequately studied in patients with breast cancer. In order to evaluate these effects, we have studied 146 patients with breast cancer treated by mastectomy at the Gustave Roussy Cancer Institute between 1965 and 1983 and who received a gel-filled silicone implant for immediate or delayed breast reconstruction between 1976 and 1984. These patients were compared with 146 matched controls with breast cancer who were treated in the same center by mastectomy without breast reconstruction and were matched for age at diagnosis (within 10 years), year of diagnosis (within 3 years), stage, histologic type of the tumor, histopathologic grade, and nodal status. The relative risks of death, relapse, and second primary cancer were estimated by means of the Cox proportional hazards model stratified on age at diagnosis. The risks of distant metastasis and death due to breast cancer were significantly lower in the breast reconstruction group than in the control group. The risks of local recurrence, second breast cancer, and second primary cancer in another site than the breast were not significantly different between the two groups of patients. Our results do not support the hypothesis of a detrimental effect of gel-filled silicone implants either in the course of breast cancer or in the risk of death due to other diseases.

Breast Neoplasms↗

Self-reported symptoms among women after cosmetic breast implant and breast reduction surgery.

A retrospective cohort study was performed in Sweden to evaluate the possibility that an individual symptom or constellation of illness symptoms related to silicone occurs in women after breast implant surgery. A random sample (n = 2500) of all women in the Swedish national implant registry who underwent breast augmentation surgery with alloplastic breast implants during the years 1965 through 1993 was compared with a sample (n = 3500) of women who underwent breast reduction surgery during the same period, frequency matched to the implant patients for age and calendar year at the time of surgery. In total, 65 percent of the breast implant patients (n = 1546) and 72 percent of the breast reduction patients (n = 2496) completed a self-administered questionnaire covering 28 rheumatologic and other symptoms and lifestyle and demographic factors. Practically all of the 28 symptoms inquired about were reported more often by women in the breast implant cohort, with 16 (57 percent) significantly more common in breast implant recipients. In contrast, few significant differences or consistent patterns were observed in the length of time since the implant and in the type (silicone or saline) or volume of the implant. Although women with breast implants report a multitude of symptoms more often than women who have breast reduction surgery, the lack of specificity and absence of dose-response relationships suggest that the excess of reported symptoms is not causally related to cosmetic implants.

Adult↗

Simultaneous endoscope-assisted contralateral breast augmentation with implants in patients undergoing postmastectomy breast reconstruction with abdominal flaps.

BACKGROUND: Unilateral breast reconstruction after mastectomy provides the challenge of achieving symmetry with the opposite side. Reduction mastopexy is a common balancing procedure for the contralateral breast used to achieve pleasing and symmetrical breasts. Although symmetry is the ultimate goal, some women have a hypoplastic and/or ptotic contralateral breast, and the recreation of this shape would therefore not be desirable. METHODS: From April of 2000 to April of 2005, a total of 158 patients underwent postmastectomy breast reconstruction using either free deep inferior epigastric perforator flaps (n = 142) or superficial inferior epigastric artery flaps (n = 16) at Chang Gung Memorial Hospital. Of the 158 patients, 19 (12.0 percent) underwent endoscope-assisted placement of implants into the contralateral breast at the same surgical stage to form a more pleasing breast mound. Mean patient age was 46.1 +/- 7.6 years. All patients had a slender body habitus, with small to medium-sized breasts. Saline-filled implants were placed in a submuscular position with the assistance of endoscopy. Five different incisions for access were used: transaxillary (n = 6), Port-A-Cath catheter scar (n = 4), inframammary (n = 1), biopsy scar (n = 1), and transmidline (n = 7). RESULTS: The success rate was 100 percent, with complete survival of the 19 flaps. In three patients, revision procedures were carried out at 12 to 44 months' follow-up because of implant leakage, capsular contracture, and nipple ptosis (one patient each). The remaining patients were highly satisfied with the cosmetic result, and symmetry was achieved, with soft, natural appearing breasts during the follow-up period of 29.2 +/- 16.9 months. The transmidline approach was superior to the other routes, because no additional scar was produced and access was easier. CONCLUSIONS: Contralateral breast augmentation at the same stage with deep inferior epigastric perforator or superficial inferior epigastric artery flap surgery can be performed with high success rates and poses no surgical risks or morbidity to patients. The combined procedure does not significantly extend the time of operation, and aesthetically pleasing results and symmetry can be achieved and sustained over the long term.

Abdomen↗

Acceptability of exclusive breast-feeding with early cessation to prevent HIV transmission through breast milk, ANRS 1201/1202 Ditrame Plus, Abidjan, Côte d'Ivoire.

OBJECTIVE: We assessed the uptake of a nutritional intervention promoting exclusive breast-feeding with early cessation between 3 and 4 months of age to reduce postnatal transmission of HIV in Abidjan, Côte d'Ivoire. DESIGN: Between March 2001 and March 2003, HIV-infected pregnant women who had received perinatal antiretroviral prophylaxis were systematically offered prenatally 2 infant feeding interventions: artificial feeding or exclusive breast-feeding during 3 months and then early cessation of breast-feeding. Mother-infant pairs were closely followed for a period of 2 years, with continuous nutritional counseling and detailed collection of feeding practices. RESULTS: Among the 557 mothers enrolled, 262 (47%) initiated breast-feeding. Of these women, the probability of practicing exclusive breast-feeding from birth was 18% and 10% at 1 and 3 months of age, respectively. Complete cessation of breast-feeding was obtained in 45% and 63% by 4 and 6 months of age, respectively. Environmental factors such as living with a partner's family were associated with failure to initiate early cessation of breast-feeding. CONCLUSIONS: Acceptability of exclusive breast-feeding was low in this urban population. Shortening the duration of breast-feeding seemed to be feasible, however. Further investigations are ongoing to evaluate the safety and effectiveness of this intervention in reducing breast milk HIV transmission.

Breast Feeding↗

Lymphedema of the arm and breast in irradiated breast cancer patients: risks in an era of dramatically changing axillary surgery.

The purpose of this study was to assess risk for lymphedema of the breast and arm in radiotherapy patients in an era of less extensive axillary surgery. Breast cancer patients treated for cure were reviewed, with a minimum follow-up of 1.5 years from the end of treatment. Clinical, surgical, and radiation-related variables were tested for statistical association with arm and breast lymphedema using regression analyses, t-tests, and chi-squared analyses. Between January 1998 and June 2001, 240 women received radiation for localized breast cancer in our center. The incidence of lymphedema of the ipsilateral breast, arm, and combined (breast and arm) was 9.6%, 7.6%, and 1.8%, respectively, with a median follow-up of 27 months. For breast edema, t-test and multivariate analysis showed body mass index (BMI) to be significant (p = 0.043, p = 0.0038), as was chi-squared and multivariate testing for site of tumor in the breast (p = 0.0043, p = 0.0035). For arm edema, t-test and multivariate analyses showed the number of nodes removed to be significant (p = 0.0040, p = 0.0458); the size of the tumor was also significant by multivariate analyses (p = 0.0027). Tumor size appeared significant because a number of very large cancers failed locally and caused cancer-related obstructive lymphedema. In our center, even modern, limited level 1-2 axillary dissection and tangential irradiation carries the risk of arm lymphedema that would argue in favor of sentinel node biopsy. For breast edema, disruption of draining lymphatics by surgery and radiation with boost to the upper outer quadrant increased risk, especially for the obese. Fortunately both breast and arm edema benefited from manual lymphatic drainage.

Adult↗

Breast cancer in limited-resource countries: an overview of the Breast Health Global Initiative 2005 guidelines.

Breast cancer is the most common cause of cancer-related death among women worldwide, with case fatality rates highest in low-resource countries. Despite significant scientific advances in its management, most of the world faces resource constraints that limit the capacity to improve early detection, diagnosis, and treatment of the disease. The Breast Health Global Initiative (BHGI) strives to develop evidence-based, economically feasible, and culturally appropriate guidelines that can be used in nations with limited health care resources to improve breast cancer outcomes. Using an evidence-based consensus panel process, four BHGI expert panels addressed the areas of early detection and access to care, diagnosis and pathology, treatment and resource allocation, and health care systems and public policy as they relate to breast health care in limited-resource settings. To update and expand on the BHGI Guidelines published in 2003, the 2005 BHGI panels outlined a stepwise, systematic approach to health care improvement using a tiered system of resource allotment into four levels-basic, limited, enhanced, and maximal-based on the contribution of each resource toward improving clinical outcomes. Early breast cancer detection improves outcome in a cost-effective fashion assuming treatment is available, but requires public education to foster active patient participation in diagnosis and treatment. Clinical breast examination combined with diagnostic breast imaging (ultrasound +/- diagnostic mammography) can facilitate cost-effective tissue sampling techniques for cytologic or histologic diagnosis. Breast-conserving treatment with partial mastectomy and radiation therapy requires more health care resources and infrastructure than mastectomy, but can be provided in a thoughtfully designed limited-resource setting. The availability and administration of systemic therapies are critical to improving breast cancer survival. Estrogen receptor testing allows patient selection for hormonal treatments (tamoxifen, oophorectomy). Chemotherapy, which requires some allocation of resources and infrastructure, is needed to treat node-positive, locally advanced breast cancers, which represent the most common clinical presentation of disease in low-resource countries. When chemotherapy is not available, patients with locally advanced, hormone receptor-negative cancers can only receive palliative therapy. Future research is needed to better determine how these guidelines can best be implemented in limited-resource settings.

Breast Neoplasms↗

Are fathers prepared to encourage their partners to breast feed? A study about fathers' knowledge of breast feeding.

In order to study fathers' knowledge of breast feeding and its relationship with paternal factors, fathers of 92 breast feeding and 89 non-breast feeding newborns were compared. Paternal factors included previous children and the way they were fed, participation in prenatal care, attendance at prenatal classes, breast feeding information provided by health professionals, use of reading materials and interest in learning more about the subject. The results indicated that fathers had poor knowledge about breast feeding, especially those whose children were being bottle fed. After adjustments for confounders, fathers who had previous breast-fed child(ren), had attended prenatal classes and who received information about breast feeding from medical personnel had a significantly higher chance of having a better knowledge of breast feeding. It seems that fathers need to be better prepared to assume their new role as breast feeding supporters. Prenatal care was shown to be a good opportunity to improve fathers' knowledge of breast feeding.

Adult↗

Effect of the method of breast feeding on breast engorgement, mastitis and infantile colic.

This exploratory study compared the effect of two methods of breast feeding on breast engorgement, mastitis, infantile colic and duration of breast feeding. An opportunity sample of subjects was assigned either to the experimental group (prolonged emptying of one breast at each feed) (n = 150) or to the control group (both breasts equally drained at each feed) (n = 152) and both groups were followed prospectively to 6 months after delivery. The experimental group had a lower incidence of breast engorgement in the first week (61.4% versus 74.3%; p < 0.02) and colic over the first 6 months (12% versus 23.4%; p < 0.02). There was no significant difference between the two groups in the incidence of mastitis over 6 months and the length of breast feeding (16.5 +/- 10.3 weeks versus 17.5 +/- 10 weeks experimental versus control group). The majority of mothers in the experimental group (63%) felt it necessary to offer the second breast at the end of a feed to satisfy their infant's hunger. The "perceived insufficient milk supply syndrome" was the main reason given for cessation of breast feeding in both groups. This study provides data to advise nursing mothers about these two methods of breast feeding.

Adult↗

Mammographic breast density as a general marker of breast cancer risk.

Mammographic breast density is a strong risk factor for breast cancer but whether breast density is a general marker of susceptibility or is specific to the location of the eventual cancer is unknown. A study of 372 incident breast cancer cases and 713 matched controls was conducted within the Mayo Clinic mammography screening practice. Mammograms on average 7 years before breast cancer were digitized, and quantitative measures of percentage density and dense area from each side and view were estimated. A regional density estimate accounting for overall percentage density was calculated from both mammogram views. Location of breast cancer and potential confounders were abstracted from medical records. Conditional logistic regression was used to estimate associations, and C-statistics were used to evaluate the strength of risk prediction. There were increasing trends in breast cancer risk with increasing quartiles of percentage density and dense area, irrespective of the side of the breast with cancer (P(trends) < 0.001). Percentage density from the ipsilateral side [craniocaudal (CC): odds ratios (ORs), 1.0 (ref), 1.7, 3.1, and 3.1; mediolateral oblique (MLO): ORs, 1.0 (ref), 1.5, 2.2, and 2.8] and the contralateral side [CC: ORs, 1.0 (ref), 1.8, 2.2, and 3.7; MLO: ORs, 1.0 (ref), 1.6, 1.9, and 2.5] similarly predicted case-control status (C-statistics, 0.64-65). Accounting for overall percentage density, density in the region where the cancer subsequently developed was not a significant risk factor [CC: 1.0 (ref), 1.3, 1.0, and 1.2; MLO: 1.0 (ref), 1.1, 1.0, and 1.1 for increasing quartiles]. Results did not change when examining mammograms 3 years on average before the cancer. Overall mammographic density seems to represent a general marker of breast cancer risk that is not specific to breast side or location of the eventual cancer.

Breast Neoplasms↗

Metastasis tumor antigen family proteins during breast cancer progression and metastasis in a reliable mouse model for human breast cancer.

PURPOSE: Chromatin remodeling pathways are critical in the regulation of cancer-related genes and are currently being explored as potential targets for therapeutic intervention. The metastasis tumor antigen (MTA) family of proteins, MTA1, MTA2, and MTA3, are components of chromatin remodeling pathways with potential roles in breast cancer. Although all three MTA family proteins have been shown to be associated with metastatic progression of breast cancers, the expression characteristic of MTA1-3 proteins in a multistep breast cancer progression model remains unknown. Structural and functional studies have suggested that they are heterogeneous in the Mi-2/NuRD complex, exhibit tissue-specific patterns of expression, and impart unique properties to estrogen receptor-alpha (ERalpha) action. This led us to hypothesize that each member of the MTA family possesses a unique role and interacts with different pathways in the stepwise process of breast cancer development and progression. EXPERIMENTAL DESIGN: MTA family proteins were examined by immunohistochemistry in breast cancer processes ranging from normal duct, to premalignant lesions, to invasive carcinoma, and to metastasized tumors in PyV-mT transgenic mice, which represents a reliable model for multistage tumorigenesis of human breast cancer. We also determined the association of MTA proteins with the status of cell proliferation, ER, E-cadherin and cytoplasmic beta-catenin, and cancer-related coactivators, AIB1 and PELP1. RESULTS: The expression of all three MTA proteins was altered in primary breast tumors. Each MTA protein had a unique expression pattern during the primary breast tumor progression. Altered expression of MTA1 was observed in both premalignant lesion and malignant carcinoma, but an elevated nuclear expression was observed in ER-negative carcinomas. MTA3 was exclusively expressed in a subset of cells of ER-positive premalignant lesions but not in carcinomas. MTA2 expression seems to be unrelated to ER status. Loss of MTA3 expression and more nuclear localization of MTA1 occurred with loss of E-cadherin and decreased cytoplasmic beta-catenin, two molecules essential for epithelial cell adhesion and important tumor cell invasion. At the late stage of tumor formation, MTA1 is usually expressed in the center of tumors. Coincidentally, the distribution of MTA1-positive cells at this stage was complementary to that of AIB1 and PELP1, which were localized to the tumor periphery with relatively active cell proliferation, scattered ER-positive cells and a limited differentiation. In metastasized lung tumors, the expression pattern of MTA-protein expression was distinct from that in primary counterparts. CONCLUSIONS: The findings presented here support the notion that each member of the MTA family might potentially play a stepwise role in a cell type-specific manner during breast cancer progression to metastasis. On the basis of the noted temporal expression patterns of MTA proteins with ER status, cell adhesion-essential regulators (E-cadherin and cytoplasmic beta-catenin), and coactivators, we propose that MTA protein-related chromatin remodeling pathways interact with steroid receptors, growth factor receptors, and other transcriptional signaling pathways to orchestrate the governing of events in breast cancer progression and metastasis.

Animals↗

Is breast cancer ever cured? Follow-up study of 5623 breast cancer patients.

The authors evaluated 5623 cases of primary breast cancer followed for 1 to 21 years. Overall and breast cancer death rates were determined and compared to expected rates. Breast cancer patients showed overall and breast cancer death rates significantly higher than expected and which persisted at long-term follow-up. The observed/expected overall death ratios for follow-up periods of 0-5, 6-10, 11-15 or 16-20 years were 3.61, 2.55, 1.60 and 2.11, respectively. Death rates from breast cancer at 5, 10, 15 and 20 years were 20%, 32%, 40% and 48% respectively. The evidence of a persistent excess mortality even after long-term follow-up suggests the hypothesis that breast cancer is a systemic disease when clinically diagnosed. This study provided no evidence of a "clinical" cure for breast cancer patients. Even for N- patients the 5, 10, 15 and 20 year death rates from breast cancer were 12%, 20%, 28% and 38%, respectively. N- breast cancer, which is currently considered as a localized disease cured by surgery in most cases, would be better regarded to as a slow-growing metastatic disease, although "personal" cure may be achieved in many subjects dying of causes other than breast cancer.

Breast Neoplasms↗

Ductal-lobar organisation of human breast tissue, its relevance in disease and a research objective: vector mapping of parenchyma in complete breasts (the Astley Cooper project).

A human breast has many lobes, which are highly variable in size and shape, each with one central duct, its peripheral branches and their associated glandular tissues. Realising the potential of new endoductal approaches to breast diagnosis and improving our understanding of breast cancer precursors will require greatly improved knowledge of this ductal-lobar anatomy and the distribution of cancer precursors within it. This architecture is very challenging to study in its entirety: whole-breast lobe mapping has only been achieved for two human breasts. Clearly, much more efficient techniques are required. Streamlined data capture and visualisation of breast parenchymal anatomy from thin and thick sections in a vector format would allow integrated mapping of whole-breast structure with conventional histology and molecular data. The 'Astley Cooper digital breast mapping project' is proposed as a name for this achievable research objective. Success would offer new insights into the development of breast cancer precursor lesions, allow testing of the important 'sick lobe' hypothesis, improve correlation with imaging studies and provide 'ground truth' for mathematical modelling of breast growth.

Breast↗

Effect of breast magnetic resonance imaging on the clinical management of women with early-stage breast carcinoma.

PURPOSE: To determine the impact of breast magnetic resonance imaging (MRI) on the clinical management of patients with early-stage breast cancer. PATIENTS AND METHODS: A review was performed of the records of 207 women with early-stage breast cancer (including five women with bilateral disease) who underwent breast MRI during work-up for breast conservation treatment. All patients presented with clinical stage 0, I, or II disease. For each patient, a determination was made whether the breast MRI affected the clinical management, and if so, whether the patient was well served by the change in management. RESULTS: The MRI findings affected the clinical management in 43 cases (20% of 212 breast cancers). Based on the pathology findings and the overall clinical course for each case, the breast MRI was judged to have had a strongly favorable effect on management in 18 cases (8%), a somewhat favorable effect in six cases (3%), an uncertain effect in five cases (2%), a somewhat unfavorable effect in 11 cases (5%), and a strongly unfavorable effect in three cases (1%). The effect of MRI was not significantly different for invasive carcinoma compared with ductal carcinoma-in-situ (all P > or =.27). However, the effect of MRI was significantly greater when the MRI was performed before an excisional biopsy (P =.0011) or for larger tumors (P =.0089). CONCLUSIONS: Breast MRI alters the clinical management for a sizable fraction of women with early-stage breast cancer and appears to offer clinically useful information for determining optimal local treatment.

Adult↗

A case-control study to estimate the impact on breast cancer death of the breast screening programme in Wales.

OBJECTIVES: The aim of this study was to estimate the effect of service screening, as provided by the NHS breast screening programme, on breast cancer mortality in Wales. Furthermore, we wished to ascertain whether a reduction in breast cancer mortality consistent with that observed in the randomised screening trials was being achieved. SETTING: The NHS Breast Screening Programme in Wales, managed by Breast Test Wales, with headquarters in Cardiff. METHODS: A case-control study design with 1:2 matching. The cases were deaths from breast cancer in women aged 50-75 years at diagnosis who were diagnosed after the instigation of screening in 1991 and who died after 1998. The controls were women who had not died of breast cancer or any other condition during the study period. One was from the same GP practice and the other from a different GP practice within the same district, matched by year of birth. RESULTS: Based on 419 cases, the odds ratio for risk of death from breast cancer for women who have attended at least one routine screen compared to those never screened was 0.62 (95% confidence interval [CI] 0.47-0.82, p=0.001). After excluding cases diagnosed prior to 1995 and adjusting for self-selection bias, the estimated mortality reduction was 25% (odds ratio=0.75, 95% CI 0.49-1.14, p=0.09). CONCLUSION: The Breast Test Wales screening programme is achieving a reduction in breast cancer mortality of 25% in women attending for screening, which is consistent with the results of the randomized controlled trials of mammographic screening.

Aged↗

Mammography in women with axillary lymphadenopathy and normal breasts on physical examination: value in detecting occult breast carcinoma.

OBJECTIVE: The purpose of this study was to determine the value of mammography in detecting occult carcinoma in patients with axillary adenopathy and normal breasts on physical examination. MATERIALS AND METHODS: We analyzed the results of mammography performed in 17 patients; all women had palpable axillary lymphadenopathy of unknown origin and all had normal breasts on physical examination. RESULTS: In 10 of the 17 patients, mammographic findings were abnormal. The mammographic finding of axillary adenopathy in seven patients was inconsequential because the nodes were evident on physical examination. Three patients had abnormal mammographic findings that were potentially significant, including one with a poorly defined mass suggestive of breast carcinoma, one with a subcutaneous nodule, and one with parenchymal breast edema. Two of 17 patients had an occult breast cancer. In only one of the patients was the cancer detected on mammography. The other patient had undergone prior left mastectomy and was thought to have metastases to the right axilla from the contralateral breast. Mammographic findings in this latter patient were normal. CONCLUSION: While occult breast carcinoma was relatively common in our series (two of 17 patients), the ability to detect the tumor with mammography was disappointing (one of two patients). This may be explained by the fact that one postmastectomy patient with occult carcinoma had metastatic disease to the contralateral axilla and a normal remaining breast, which was pathologically confirmed at mastectomy. Our experience suggests that mammography is valuable in patients with normal breasts on physical examination who have primary carcinoma involving ipsilateral axillary lymph nodes. The procedure should be included in the diagnostic evaluation of patients with axillary adenopathy in order to detect the unusual case of occult breast carcinoma.

Axilla↗

Human glandular kallikrein in breast milk, amniotic fluid, and breast cyst fluid.

BACKGROUND: Human glandular kallikrein (hK2) belongs to the serine protease family of enzymes and has high sequence homology with prostate-specific antigen (PSA). The physiological role of hK2 has not as yet been determined, but there is evidence that it can regulate the proteolytic activity of PSA through processing and activating pro-PSA, an inactive precursor. Thus, it is conceivable that these two secreted proteins may coexist in biological fluids. Currently, hK2 is considered an androgen-regulated and prostate-specific protein. Recently, it has been demonstrated that hK2 is expressed in the breast cancer cell line T-47D after stimulation by steroid hormones, and we reported that hK2 can be detected in a subset of breast tumor extracts. These data suggest that hK2 may be expressed in tissues other than the prostate, such as those in which PSA has already been detected. Because hK2 is a secreted protein, it may be present in various biological fluids. METHODS: We analyzed milk samples from lactating women, amniotic fluid from pregnant women, and breast cyst fluid from patients with gross breast cystic disease, using a highly sensitive and specific immunoassay for hK2. RESULTS: hK2 was present in all three biological fluids. We suggest that the female breast may produce hK2 and provide evidence that hK2 may have value as an additional marker for the discrimination between type I and type II breast cysts. CONCLUSIONS: The female breast produces hK2 in addition to PSA. More studies are necessary to establish the role of this kallikrein in nondiseased breast, gross breast cystic disease, and breast cancer.

Amniotic Fluid↗

Breast cancer patterns and lifetime risk of developing breast cancer among Puerto Rican females.

OBJECTIVES: The purpose of this study was to evaluate the epidemiologic patterns of breast cancer and to estimate the lifetime risk probability of developing breast cancer among Hispanic females using cancer data from Puerto Rico. BACKGROUND: The age-adjusted breast cancer incidence rate (per 100,000) in Puerto Rico increased from 15.3 in 1960-1964 to 43.3 in 1985-1989. The age-adjusted breast cancer mortality rate (per 100,000) increased from 5.7 to 10.6 comparing the same two time periods (1960-1964 vs 1985-1989). Nevertheless, in 1985-1989 breast cancer incidence rate was higher in US White females (110.8 per 100,000) compared to Puerto Rican females (51.4 per 100,000; age-adjusted to the 1970 US standard population). The breast cancer mortality rate was also higher in US White females (27.4 per 100,000) than in Puerto Rican females (15.1 per 100,000; age-adjusted to the 1970 US standard population) during 1985-1989. METHODS: A multiple decrement life table was constructed applying age-specific incidence and mortality rates from cross-sectional data sets (1980-1984 and 1985-1989 data for Puerto Rican females and 1987-1989 SEER data sets for US White and Black females) to a hypothetical cohort of 10,000,000 women. The probability of developing invasive breast cancer was computed for the three groups using the long version of DEVCAN: Probability of DEVeloping CANcer software, version 3.3. RESULTS: The lifetime risk of developing breast cancer was 5.4% for Puerto Rican females, compared to 8.8% for US Black females and 13.0% for US White females. Lifetime risk for Puerto Rican females increased from 4.5% in 1980-1984 to 5.4% in 1985-1989. CONCLUSIONS: Lifetime risk of breast cancer appears to be increasing in Puerto Rico, but remains lower than the probability for US White females. Therefore, the application of lifetime probability of developing invasive breast cancer estimated for the US female population will overestimate the risk for the Puerto Rican female population.

Adolescent↗