Showing papers on "Breast cancer published in 1988"
TL;DR: Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.
Abstract: STUDY OBJECTIVE--To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN--Birth year cohorts of city population separately randomised into study and control groups. SETTING--Screening clinic outside main hospital. PATIENTS--Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS--Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT--Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS--All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS--In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS--Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.
887 citations
TL;DR: It is concluded that neu overexpression may be an early step in the development of a distinct histologic type of carcinoma of the breast, but it could find no association of overeexpression with lymph-node status or tumor recurrence.
Abstract: Amplification of the neu proto-oncogene in breast cancer has been reported to correlate with the presence of lymph-node metastases and with a poor prognosis. We describe a method for the immunohistochemical detection of overexpression of neu protein on formalin-fixed paraffin-embedded tissue, with the use of two different monoclonal antibodies. In a group of tumors with a known neu-gene copy number, intense membrane staining of tumor cells was present in all tumors with neu-gene amplification. Of 189 tumors from patients with Stage II breast cancer, 27 (14 percent) had neu-membrane staining. Neu overexpression was associated with larger tumor size (P = 0.006) but not with lymph-node involvement. Neu-protein expression in lymph-node metastases was the same as its expression in primary tumors. Among the patients with neu overexpression (median follow-up, 37 months), disease-free survival was not significantly shorter; overall survival was reduced significantly in these patients (P = 0.042), but thi...
869 citations
Book•
01 Sep 1988
TL;DR: Anatomy of Breast Development, Stages of Breast development, and Sarcomas of the Breast: Major Histological Types.
Abstract: Anatomy. Stages of Breast Development. The Male Breast and Gynaecomastia. Cysts and Apocrine Change. Adenosis. Miscellaneous Non-Neoplastic Conditions. Fibroadenoma and Related Changes. Columnar Alteration of Lobules. Radial Scars and Complex Sclerosing Lesions. Papilloma and Related Lesions. Epithelial Hyperplasia. Carcinoma in Situ (CIS). Infiltrating Carcinoma: Major Histological Types. Uncommon Types of Invasive Carcinoma. Rare Patterns of Invasive Carcinoma. Miscellaneous Features of Carcinoma. Grading of Invasive Carcinoma of the Breast. Non-Intrinsic Tumours. Metastasis of Breast Cancer. Sarcomas of the Breast
702 citations
TL;DR: It is suggested that as many as one in five women with breast cancer may carry the AT gene and that the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients.
Abstract: Ataxia-telangiectasia (AT) is a human autosomal recessive disorder of childhood1,2 characterized by: (1) progressive cerebellar ataxia with degeneration of Purkinje cells; (2) hypersensitivity of fibroblasts and lymphocytes to ionizing radiation3; (3) a 61-fold and 184-fold increased cancer incidence in white and black patients, respectively4; (4) non-random chromosomal rearrangements in lymphocytes; (5) thymic hypoplasia with cellular and humoral (IgA and IgG2) immunodeficiencies; (6) elevated serum level of alphafetoprotein; (7) premature ageing; and (8) endocrine disorders, such as insulin-resistant diabetes mellitus. A DNA processing or repair protein is the suspected common denominator in this pathology5. Heterozygotes are generally healthy; however, the sensitivity of their cultured cells to ionizing radiation is intermediate between normal individuals and that of affected homozygotes6. Furthermore, heterozygous females are at an increased risk of breast cancer7,8. These findings, when coupled with an estimated carrier frequency of 0.5–5.0%, suggest that (1) as many as one in five women with breast cancer may carry the AT gene7 and that (2) the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients10. To identify the genetic defect responsible for this multifaceted disorder, and to provide effective carrier detection, we performed a genetic linkage analysis of 31 families with AT-affected members. This has allowed us to localize a gene for AT to chromosomal region 11q22-23.
636 citations
TL;DR: Both hypotheses suggest that the risk of breast cancer could be reduced by delaying the onset of regular ovulatory menstrual cycles and by minimizing the therapeutic use of oestrogens, and possibly of progestagens, in postmenopausal women.
625 citations
Journal Article•
TL;DR: This is the first study showing that a determination of the level of c-erbB-2 protein in paraffin-embedded tumor sections may have prognostic value for the course of human breast cancer.
Abstract: Fifty-one primary human breast tumors were analyzed for amplification of the c-erbB-2 protooncogene. Thirteen (25%) of the DNA samples contained multiple gene copies. Paraffin-embedded tumor sections, available from 47 of the cases, were stained with a c-erbB-2 specific antiserum. Eighty-three % (10 of 12) of the tumors containing amplified c-erbB-2 gene copies stained positively with the c-erbB-2 specific antiserum (P = 0.03). Thirteen tumors containing single copy c-erbB-2 sequences also stained positively with the antiserum. This suggests that mechanisms other than gene amplification may lead to elevated levels of c-erbB-2 protein. Finally, there was a statistically significant correlation between c-erbB-2 protein expression and parameters used in breast cancer prognosis. Positive staining was associated with positive nodal status of the patient (P = 0.02) and with tumors showing a poor nuclear grade (P = 0.02). This is the first study showing that a determination of the level of c-erbB-2 protein in paraffin-embedded tumor sections may have prognostic value for the course of human breast cancer.
596 citations
TL;DR: Evidence for a highly penetrant, autosomal dominant susceptibility allele for breast cancer in a high-risk family and the general population suggests that high- risk families can serve as models for understanding breast cancers in the population as a whole.
Abstract: Segregation analysis of breast cancer in families can provide the logical basis and the specific genetic models for mapping and identifying genes responsible for human breast cancer Patterns of breast cancer occurrence in families were investigated by complex segregation analysis In a sample of 1579 nuclear families ascertained through a population-based series of probands, an autosomal dominant model with a highly penetrant susceptibility allele fully explained disease clustering From the maximum-likelihood Mendelian model, the frequency of the susceptibility allele was 00006 in the general population, and lifetime risk of breast cancer was 082 among susceptible women and 008 among women without the susceptibility allele Inherited susceptibility affected only 4% of families in the sample: multiple cases of this relatively common disease occurred in other families by chance The same genetic models, with higher gene frequency, explained disease clustering in an extended kindred at high risk of breast cancer Evidence for a highly penetrant, autosomal dominant susceptibility allele for breast cancer in a high-risk family and the general population suggests that high-risk families can serve as models for understanding breast cancer in the population as a whole
482 citations
TL;DR: The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment, and this multidisciplinary approach to locally advanced breast cancer rendered most patients disease‐free and produced an excellent local control rate.
Abstract: One hundred seventy-four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed. Subsequently, adjuvant chemotherapy was continued. There were 48 patients with Stage IIIA, and 126 patients with Stage IIIB disease. A complete remission was achieved in 16.7% of the patients, and 70.7% achieved a partial remission after the initial three cycles of FAC. The complete response rate was higher for patients with Stage IIIA, than for patients with Stage IIIB disease. All but six of the 174 patients treated were rendered disease-free after induction chemotherapy and local treatment. The median follow-up of this group of patients is 59 months. The 5-year disease-free survival rates were 84% for patients with Stage IIIA, and 33% for patients with Stage IIIB disease. The 5-year survival rate for, patients with Stage IIIA was 84%, and for patients with Stage IIIB 44%. At 10 years, 56% of patients with Stage IIIA and 26% of patients with Stage IIIB disease are projected to be alive. Younger patients, and those with estrogen receptor-positive tumors, had a trend for better survival than older patients and those with estrogen receptor-negative tumors. The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment. Twenty-six patients (15.3%) had locoregional recurrence. This multidisciplinary approach to locally advanced breast cancer rendered most patients disease-free and produced an excellent local control rate. Modifications of this treatment strategy may result in further improvement of survival rates.
482 citations
TL;DR: A significant increase in the disease-free survival of postmenopausal women treated with tamoxifen is shown, particularly in patients with hormone-receptor-positive tumors.
Abstract: Tamoxifen, an antiestrogen, is a competitive inhibitor of estradiol, blocking its effects on the target organs. During the 10 years it has been used in the United States it has become pref...
466 citations
TL;DR: This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.
Abstract: Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 X 10(9) to 2.3 X 10(11) cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.
433 citations
TL;DR: It is disclosed that in node negative breast cancer patients, NG is a better marker of prognosis than is tumor ER, and that PR is of little or no value.
Abstract: This study correlates the disease-free survival (DFS), distant disease-free survival (DDFS), and survival (S) of 1,157 histologically node negative breast cancer patients with the estrogen and/or progesterone receptor (ER, PR) and with the nuclear or histologic grade (NG, HG) of their tumors. All were treated by operation without systemic adjuvant therapy. The DFS, DDFS, and S were significantly greater (P = .005, .004, less than .001) in patients with ER positive than ER negative tumors but the magnitude of the differences after 5 years of follow-up was slight (8% in both DFS and DDFS and 10% in S). Differences of that magnitude are insufficient to discriminate clearly between patients who should or should not receive systemic therapy. As with ER, there were outcome differences in favor of PR positive tumors but only in S was the difference significant (8% at 5 years; P = .002). When combined with ER, PR made no independent contribution in the outcome prediction. Regression analysis indicated that NG was...
TL;DR: It is suggested that chemotherapy contributes to thrombosis in patients with breast cancer.
Abstract: Thromboembolic disease has long been recognized as a complication of cancer. Recent reports have suggested that drugs used in the treatment of cancer, including chemotherapeutic agents and hormones, may contribute to this risk, but it has not been possible to separate the effect of these drugs from that of the cancer. We performed a randomized trial comparing 12 weeks of chemohormonal therapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, doxorubicin, and tamoxifen) with 36 weeks of chemotherapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone) in patients with Stage II breast cancer. Among 205 patients randomly assigned to treatment, there were 14 episodes of thrombosis (6.8 percent). These 14 episodes occurred during 979 patient-months of chemotherapy; by comparison, there were no events during 2413 patient-months without therapy. During the first 12 weeks of the study, five patients in the 12-week group and four patients in the 36-week group had thrombosis. During the subsequent 24 weeks, when only patients in the 36-week group were still receiving chemotherapy, there was no thrombosis in the 12-week group, but there were five additional events in the 36-week group (P = 0.03). These findings suggest that chemotherapy contributes to thrombosis in patients with breast cancer.
TL;DR: Risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages, and radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia.
Abstract: The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder (relative risk (RR) = 4.0), rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer wasmore » observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors.« less
TL;DR: PET images demonstrated uptake of the labeled estrogen analog at sites of primary carcinomas and in several foci of axillary lymph node metastases, as well as in one distant metastatic site, suggesting this technique may provide an in vivo method of assessing estrogen receptors in primary and metastatic breast cancers.
Abstract: Thirteen patients with primary breast masses were studied with positron emission tomography (PET) and 16 alpha-[fluorine-18]-fluoroestradiol-17 beta. PET images demonstrated uptake of the labeled estrogen analog at sites of primary carcinomas and in several foci of axillary lymph node metastases, as well as in one distant metastatic site. There was excellent correlation between uptake within the primary tumor measured on the PET images and the tumor estrogen-receptor concentration measured in vitro after excision (r = .96). This technique may provide an in vivo method of assessing estrogen receptors in primary and metastatic breast cancers and thus guide management of this disease with antiestrogen chemotherapy.
TL;DR: There was strong evidence to support a dose-response relation in both the case-control and follow-up epidemiologic data, and this is interpreted as strongly supportive of an association between alcohol consumption and risk of breast cancer.
Abstract: Epidemiologic findings regarding the relation between alcohol consumption and risk of breast cancer have been inconsistent. We performed a meta-analysis (a quantitative review) of the available data. To evaluate whether there was a dose-response relation between alcohol consumption and risk of breast cancer, we fitted mathematical models to the pooled data. There was strong evidence to support a dose-response relation in both the case-control and follow-up epidemiologic data. Using the dose-response curves that we calculated, the risk of breast cancer at an alcohol intake of 24 g (1 oz) of absolute alcohol daily (about two drinks daily) relative to nondrinkers was 1.4 (95% confidence interval, 1.0 to 1.8) in the case-control data and was 1.7 (95% confidence interval, 1.4 to 2.2) in the follow-up data. We interpret these findings not as proof of causality, but as strongly supportive of an association between alcohol consumption and risk of breast cancer. ( JAMA 1988;260:652-656)
Journal Article•
TL;DR: Other areas of current research reviewed here include radiation, mammographic parenchymal patterns, a high-fat diet, use of oral contraceptives (OCs), use of estrogen replacement therapy, and endogenous hormones, which do not appear promising as potential etiologic agents.
Abstract: Summary of Suggestions for Future Directions This brief review of results of recent epidemiological investigations suggests some additional approaches for future studies. First, the studies of the DES-exposed women and of oral contraceptive users suggest that the timing of exposure may be critical, since the possible effect of both these hormonal agents may be limited to specific time periods of rapid breast development. Studies of other possible etiological agents should also try to focus more on exposures during critical time periods. On the other hand, if such a critical period does not exist in postmenopausal women, then there may be little effect of hormones used at this time. Instead, exposure to higher than average levels of estrogen from estrogen replacement therapy or through greater conversion to estrogen in adipose tissue in obese women may result in only a modest elevation in risk and only after prolonged exposure, because of the relative inactivity of the breast at the time of exposure. Also, the effect of radiation and the possible effects of estrogen replacement therapy and oral contraceptives remind us of the long latency period that may be necessary before an effect is seen for at least some agents. Thus, studies with long-term follow-up and that include long-term users are important in studies of effects of hormones and other exposures. Among the newly hypothesized etiological agents, it would seem that the possible protective effect of physical activity merits further study. An effect of physical activity has not been well studied in the past, and possible biological mechanisms have been postulated. With regard to alcohol, assessment of the influence of age when consumption began and duration of exposure as well as the identification of plausible mechanisms of action would aid in clarifying the role of alcohol consumption in breast cancer etiology. Ongoing studies of benign breast diseases are aimed at addressing the question of subgroups at particularly high risk, and ongoing studies of radiation are addressing such questions as the risks from low-dose exposures and the latency period following exposure. The results of these studies will be awaited with interest. Since it is virtually certain that endogenous sex hormones play a role in breast cancer etiology, continued study of their role with new and improved measurement techniques is obviously of high priority. Likewise, in those cases of breast cancer in which marked familial aggregation is seen, newly developed probes for marker genes will be useful. Finally, it is also likely that exposures not studied to date are involved in breast cancer etiology, since known risk factors by no means account for the entire risk of breast cancer. Thus, new ideas are needed, particularly regarding exposures at critical time periods.
TL;DR: Patients and husbands differed significantly in the levels of support they perceived over time; husbands perceived less support from friends, nurses, and physicians.
Abstract: Data were obtained from 50 mastectomy patients and their husbands at 3 days and 30 days postsurgery to determine the nature of the relationship between social support and the adjustment of mastectomy patients and their husbands over time. Psychosocial adjustment was related to both patients' and husbands' levels of social support. Patients and husbands who reported higher levels of social support reported fewer adjustment difficulties at both 3 days and 30 days postsurgery. Patients and husbands differed significantly in the levels of support they perceived over time; husbands perceived less support from friends, nurses, and physicians. This study underscores the importance of assessing the support resources of both patients and husbands over time.
TL;DR: The authors conclude that the risk of developing breast cancer varies by category of benign breast disease and is directly related to the degree of epithelial atypia.
Abstract: The authors studied the relation between benign breast disease and subsequent breast cancer in 16,692 women with biopsy-diagnosed benign breast disease who had participated in the Breast Cancer Detection Demonstration Project throughout the United States. Women were classified into one of five benign breast disease categories: atypical hyperplasia, proliferative disease without atypia, nonproliferative disease, fibroadenoma, and other benign breast disease. A total of 485 incident cases of breast cancer were identified in the women from August 1973 to February 1986 after a median follow-up period of 8.3 years from the diagnosis of benign breast disease. Age-adjusted incidence rates were calculated for benign breast disease types stratified by family history and calcification status. Relative risk (RR) estimates of breast cancer for women in the five benign breast disease categories, compared with the screened women who did not develop recognizable breast disease (normal subjects), were computed using the proportional hazards model. Results indicated that risk was associated with the degree of epithelial atypia. Over all age groups, women with nonproliferative disease, proliferative disease without atypia, and atypical hyperplasia displayed progressively increasing risks of 1.5, 1.9, and 3.0, respectively, compared with normal subjects, with 95% confidence intervals (CI) exceeding unity. Particularly high risk was seen among women under age 46 years with atypical hyperplasia (RR = 5.7, 95% CI 3.0-10.6). Women with fibroadenoma as the only indication of their benign breast disease had a relative risk of 1.7, with a lower 95% confidence limit of 1.0. No increased risk was seen for women with other benign breast disease. Positive family history (RR = 1.8) and calcification (RR = 1.2) significantly increased a woman's risk proportionately over the risk associated with each benign breast disease subtype. The authors conclude that the risk of developing breast cancer varies by category of benign breast disease and is directly related to the degree of epithelial atypia.
TL;DR: Frequency of support from all sources decreased as time from surgery passed, whilst satisfaction with support varied with the type of support given and the source from which it was received; quite different patterns emerged in support needs from professional and non-professional sources.
TL;DR: One of the first major randomized trials in cancer therapy was concerned with the value of postoperative adjuvant radiotherapy for breast cancer, but the impact of this treatment on long-term survival still remains clouded.
Abstract: One of the first major randomized trials in cancer therapy was concerned with the value of postoperative adjuvant radiotherapy for breast cancer. Since then, a large number of trials have addressed this issue, but the impact of this treatment on long-term survival still remains clouded. This is due partly to the long natural history of breast cancer and partly to the changing approach to primary treatment, where a trend toward less surgery and more radiotherapy has taken place. The current interest in procedures aimed at breast conservation (Calle et al. 1978; Hell- man et al. 1980; Veronesi et al. 1981; Fisher et al. 1985 a) highlights this shift and emphasizes the need for a greater understanding of the role of radiotherapy in primary management.
TL;DR: It is concluded that urokinase‐plasminogen activator may be a new prognostic marker in breast cancer.
Abstract: Plasminogen activator is a serine protease which exists in two forms, known as tissue-type plasminogen activator and urokinase-type plasminogen activator. Here, we show that urokinase-type plasminogen activator activity in primary breast carcinomas correlates with both size of tumor and number of axillary nodes with metastases. Patients with primary carcinomas containing high levels of urokinase-type plasminogen activator activity had a significantly shorter disease-free interval than patients with low levels of activity. It is concluded that urokinase-plasminogen activator may be a new prognostic marker in breast cancer.
TL;DR: The reduced breast cancer mortality in the study group appears to result from lower mortality in stage I cases as well as from earlier case detection, and this may explain differences between the two age-at-entry cohorts in the length of follow-up time required to demonstrate a mortality reduction due to screening.
Abstract: The Health Insurance Plan (HIP) of Greater New York conducted a clinical trial to determine if screening for breast cancer with mammography and clinical examination would decrease breast cancer mortality. The extent of disease at diagnosis among breast cancers detected by screening and the effect of screening on breast cancer mortality have been evaluated in the cohort of all HIP women diagnosed with breast cancer within 6 years of entry into the trial and followed at least 18 years after trial entry. Six years was the earliest time at which the number of cases diagnosed in the control group was equal to the number of cases diagnosed in the study group. In the cohorts of women 40-49 and 50-64 years of age at entry, shifts were significant to lower stages for screen-detected cases. As a result, the study group women in each age cohort had significantly lower breast cancer mortality than control group women when statistical analyses were restricted to data from cases only. In the 40-49 age-at-entry cohort, the reduced breast cancer mortality in the study group appears to result from lower mortality in stage I cases as well as from earlier case detection, and this may explain differences between the two age-at-entry cohorts in the length of follow-up time required to demonstrate a mortality reduction due to screening.
Journal Article•
TL;DR: This study demonstrates a clear beneficial effect on breast cancer risk of lactation in a population characterized by a long cumulative duration of nursing in the majority of women, and supports several other recent reports of a residual and beneficial effect of parity on Breast cancer risk after controlling for age at first full term pregnancy.
Abstract: Five hundred thirty-four histologically confirmed incident cases of breast cancer in Chinese women of Shanghai and an equal number of age and sex-matched population controls were interviewed as part of an epidemiological study of breast cancer risk factors. Early age at menarche was positively associated with breast cancer risk whereas early age at first full term pregnancy, high parity, and long duration of nursing were each negatively associated. We found high average body weight to be a risk factor, especially among women over age 60. Use of oral contraceptives after age 45 also was a risk factor, but use in general was not. Personal history of benign breast disease and history of breast cancer in first degree female relatives both increased risk. Multivariate analysis showed that each of these risk (or protective) factors was independently related to breast cancer. In addition to confirming most of the breast cancer risk factors of Western populations in a low risk developing Asian country, this study demonstrates a clear beneficial effect on breast cancer risk of lactation in a population characterized by a long cumulative duration of nursing in the majority of women. Finally, this study supports several other recent reports of a residual and beneficial effect of parity on breast cancer risk after controlling for age at first full term pregnancy.
TL;DR: Bilateral oophorectomy at an early age exerted a protective influence on breast cancer risk and was associated with a lowered risk relative to natural menopause at a comparable age, which may reflect the more pronounced and sudden decline in endogenous hormones associated with the surgery.
Abstract: A case control study of 2,908 breast cancer cases and 3,180 controls, derived from a nationwide screening program, enabled evaluation of the relationship of breast cancer risk to a variety of menstrual factors. Risk was significantly inversely related to age at menarche, with women who first menstruated at age 15 or later having a 23% lower risk than those with menarche prior to the age of 12. There was a higher relative risk (1.3) for premenopausal than menopausal women. In contrast to previous studies, there was only a slight increase in risk associated with a late age at natural menopause, possibly owing to errors in recall. Bilateral oophorectomy at an early age exerted a protective influence on breast cancer risk, with effects manifested approximately 10 to 15 years after oophorectomy. Women who had both ovaries removed prior to the age of 40 had a 45% reduced risk compared to women with a natural menopause at ages 50 to 54. In addition, bilateral oophorectomy at an early age was associated with a lowered risk relative to natural menopause at a comparable age, which may reflect the more pronounced and sudden decline in endogenous hormones associated with the surgery. Although these results were based on patient reports regarding the types of surgical menopause experienced, validation against medical records showed close correspondence regarding the number of ovaries removed.
Journal Article•
TL;DR: It is suggested that in breast cancer IGF-II is produced by stromal tissue elements and potentially by the malignant epithelial cells, therefore, IGF- II may function as an autocrine or a paracrine growth factor in different breast tumors.
Abstract: Insulin-like growth factor II is a growth factor important in fetal development. Several cancer tissues and cell lines have been reported to express IGF-II and rat IGF-II is mitogenic for breast cancer cell lines. Using Northern analysis and ribonuclease protection assays, IGF-II mRNA was detected in normal fibroblasts and in the established breast cancer cell line, T47D. In this cell line, steady state levels of IGF-II message were increased by treatment with estradiol. 10 nm IGF-II, purified from human serum, was mitogenic for breast cancer cell lines. In vitro, IGF-II may act as an autocrine growth factor for some cell lines. RNA derived from breast cancer, pathologically normal breast tissue, and benign breast disease also contained IGF-II mRNA. When paired samples of normal and cancer tissue were obtained from the breast of the same patient, the level of IGF-II mRNA expression in the normal tissue was at least that found in the cancer. This is consistent with previous observations that show IGF-II is expressed in mesenchyme. These findings suggest that in breast cancer IGF-II is produced by stromal tissue elements and potentially by the malignant epithelial cells. Therefore, IGF-II may function as an autocrine or a paracrine growth factor in different breast tumors.
TL;DR: It is suggested that women who are older, uninsured, or lower in socioeconomic status are at an increased risk for not receiving preventive care, and that screening mammography, although more common than a decade ago, is still markedly underused.
Abstract: • To evaluate the adequacy of cervical and breast cancer screening in the United States, data were analyzed from a 1986 nationwide telephone survey (n=4659) Papanicolaou smears within the recommended three- to five-year interval were reported by 79% of women aged 20 years or older Within the preceding year, 55% of women aged 40 years or older had breast examinations performed by physicians, and 20% of women aged 50 years or older had mammograms Women who were uninsured or lower in socioeconomic status were less likely to have each of these three preventive measures, independent of the age, health status, and frequency of physician visits of the respondent In addition, women aged 50 years or older were less likely to have had Papanicolaou smears (63% vs 89%) and breast examinations (52% vs 68%) than those women aged 20 to 49 years These findings suggest that women who are older, uninsured, or lower in socioeconomic status are at an increased risk for not receiving preventive care, and that screening mammography, although more common than a decade ago, is still markedly underused ( Arch Intern Med 1988;148:1177-1181)
TL;DR: In this article, the authors found that the highest frequency of allele loss (61%) was found with the probe YNZ22, which detects a sequence on the short arm of chromosome 17 (at p13.3).
Journal Article•
TL;DR: Patients in whom distant metastases developed relatively soon after the initial diagnosis had the same postmetastatic prognosis patients whose disease metastasized later.
Abstract: From 1969 to 1977, metastatic disease developed in 145 of the 558 patients treated for breast cancer at the University of Maryland Medical System. The most common first site of distant spread was bone (51%), followed by lung (17%), brain (16%), and liver (6%). The remaining 10% of patients had multiple metastatic sites. Fewer than 10% of the entire group received adjuvant chemotherapy after primary treatment. When metastatic disease appeared, most patients had palliative systemic chemotherapy and/or irradiation. In general, patients with initially negative axillary nodes had a longer median time until relapse (development of metastatic disease) and a longer survival time after diagnosis of metastases than patients with initially positive nodes. Liver was the least common initial metastatic site; while liver metastasis was seen only in patients with positive axillary nodes, it carried the worst prognosis. The overall median survival time after metastasis was 12 months for bone and lung lesions, three months for brain lesions, and only one month for liver metastasis. The median survival of patients with multiple metastatic sites was 7.5 months. No correlation was found between time until relapse and survival after metastasis. Patients in whom distant metastases developed relatively soon after the initial diagnosis had the same postmetastatic prognosis as patients whose disease metastasized later. No correlation was found between age at initial diagnosis and metastasis-free interval or survival after metastasis.
TL;DR: Two quantitative methods, Confidence Profiles and CAN*TROL, are used to analyze evidence and estimate the health and economic consequences of adding annual mammography to annual breast physical examinations in asymptomatic women aged 40 to 49 years who are at average risk for breast cancer.
Abstract: Two quantitative methods, Confidence Profiles and CAN*TROL, are used to analyze evidence and estimate the health and economic consequences of adding annual mammography to annual breast physical examinations in asymptomatic women aged 40 to 49 years who are at average risk for breast cancer. Such women have about a 128 in 10 000 chance of having breast cancer in the next ten years and about an 82 in 10 000 chance of dying of such a cancer. Adding annual mammograms to annual breast physical examinations each year during that age decade would reduce the probability of death to about 60 in 10 000, a reduction of about 26%. Screening would increase the expected lifetime of a woman destined to get breast cancer between ages 40 and 49 years by about 3.5 years. Ten years of screening with mammography in that age decade carries a risk of radiation-induced cancer of about one in 25 000 and a risk of a surgery recommendation for a lesion that is not cancer of about one in ten. If 25% of the women in this age group in the United States were screened every year, breast cancer mortality in the year 2000 would be decreased by about 373 deaths. In 1984 dollars, the cost of screening, workups, and continuing care in the year 2000 would be about $408 million. Treatment costs would be decreased by about $6 million, leaving a net increase in costs in the year 2000 of approximately $402 million (1984 dollars). (JAMA1988;259:1512-1519)
TL;DR: Evidence is provided for a protective role of adolescent obesity against premenopausal breast cancer, and for an enhancing role of a positive energy balance during adult life on postmenopausal Breast cancer.
Abstract: The inconclusive findings of past analytic epidemiologic studies on diet and breast cancer may have resulted from the inability of these studies to assess early dietary exposures. The role of macronutrient intake during early life can be indirectly studied, however, by examining past and present body size. The authors identified by computer linkage a population-based historical cohort of 38,084 women born between 1918 and 1943, on whom information about weight and height had been recorded in Hawaii in both 1942-1943 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 607 incident cases of breast cancer for 1972-1983. An average of 4.4 cancer-free controls were matched to each case on year and month of birth and race of the parents. A matched case-control analysis, conducted in each five-year birth cohort, revealed a negative association of adolescent body mass to premenopausal breast cancer. This negative association was statistically significant in girls aged 10-14 years in 1942 (p for trend, 0.004), was present in all ethnic groups, and was strongest among overweight young women who remained overweight in adulthood. Early-age weight, height, and body surface area were not associated with either pre- or postmenopausal breast cancer. Adult weight and gain in body mass since 1942 were positively associated with postmenopausal breast cancer risk. Adjustment for age at first birth, parity and socioeconomic indicators for 1942 and 1972 did not modify the results. This study provides evidence for a protective role of adolescent obesity against premenopausal breast cancer, and for an enhancing role of a positive energy balance during adult life on postmenopausal breast cancer.