Showing papers on "Breast cancer published in 1991"
TL;DR: The results demonstrate that this method for histological grading provides important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained.
Abstract: Morphological assessment of the degree of differentiation has been shown in numerous studies to provide useful prognostic information in breast cancer, but until recently histological grading has not been accepted as a routine procedure, mainly because of perceived problems with reproducibility and consistency. In the Nottingham/Tenovus Primary Breast Cancer Study the most commonly used method, described by Bloom & Richardson, has been modified in order to make the criteria more objective. The revised technique involves semiquantitative evaluation of three morphological features--the percentage of tubule formation, the degree of nuclear pleomorphism and an accurate mitotic count using a defined field area. A numerical scoring system is used and the overall grade is derived from a summation of individual scores for the three variables: three grades of differentiation are used. Since 1973, over 2200 patients with primary operable breast cancer have been entered into a study of multiple prognostic factors. Histological grade, assessed in 1831 patients, shows a very strong correlation with prognosis; patients with grade I tumours have a significantly better survival than those with grade II and III tumours (P less than 0.0001). These results demonstrate that this method for histological grading provides important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained. Histological grade forms part of the multifactorial Nottingham prognostic index, together with tumour size and lymph node stage, which is used to stratify individual patients for appropriate therapy.
5,575 citations
TL;DR: It is concluded that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study, and is conducting a phase I trial of taxol plus doxorubicin.
Abstract: Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).
930 citations
Journal Article•
TL;DR: Segregation analysis and goodness-of-fit tests of genetic models provide evidence for the existence of a rare autosomal dominant allele (q = .0033) leading to increased susceptibility to breast cancer.
Abstract: The familial risk of breast cancer is investigated in a large population-based, case-control study conducted by the Centers for Disease Control. The data set is based on 4,730 histologically confirmed breast cancer cases aged 20 to 54 years and on 4,688 controls who were frequency matched to cases on the basis of both geographic region and 5-year categories of age, and it includes family histories, obtained through interviews of cases and controls, of breast cancer in mothers and sisters. Segregation analysis and goodness-of-fit tests of genetic models provide evidence for the existence of a rare autosomal dominant allele (q = .0033) leading to increased susceptibility to breast cancer. The effect of genotype on the risk of breast cancer is shown to be a function of a woman's age. Although, compared with noncarriers, carriers of the allele appear to be at greater risk at all ages, the ratio of age-specific risks is greatest at young ages and declines steadily thereafter. The proportion of cases predicted to carry the allele is highest (36%) among cases aged 20-29 years. This proportion gradually decreases to 1% among cases aged 80 years or older. The cumulative lifetime risk of breast cancer for women who carry the susceptibility allele is predicted to be high, approximately 92%, while the cumulative lifetime risk for noncarriers is estimated to be approximately 10%.
915 citations
TL;DR: Cancer rates were significantly higher in the group of blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the ataxia-telangiectasia gene, which predisposes heterozygotes to cancer, particularly breast cancer in women.
Abstract: Background. Ataxia—telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age—matched subjects. Retrospective studies have shown that persons heterozygous for the ataxia—telangiectasia gene, who make up about 1 percent of the general population, also have an excess risk of cancer, particularly breast cancer in women. Patients with ataxia—telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation. Methods. Cancer incidence and mortality, mortality from ischemic heart disease, and mortality from all causes were compared prospectively for a mean of 6.4 years in 1599 adult blood relatives of patients with ataxia—telangiectasia and 821 of their spouses, who served as controls, in 161 families affected by ataxia—telangiectasia. In a case–control substudy, we compared documented occupational and fluoroscopic diagnostic exposures to radiation in th...
898 citations
TL;DR: It is suggested that environmental factors in early life rather than in later life are important in the etiology of breast cancer and that later life events can substantially impact the likelihood of developing clinically detectable prostate cancer.
Abstract: Using age-adjusted incidence rates and proportional incidence ratios, the risks of prostate cancer and breast cancer in three racial/ethnic groups - Spanish-surnamed whites, other whites and Japanese - were studied in Los Angeles County native residents and compared with those in immigrants and representative 'homeland' populations. An algorithm based on social security numbers was developed and utilised to estimate age at immigration for non-US-born Los Angeles County cancer patients. For prostate cancer, the incidence rates in Los Angeles County were much higher than those in the homelands for each racial/ethnic group. However, prostate cancer rates of immigrants were similar to those of US-born patients in the Spanish-surnamed white and Japanese populations, regardless of age at immigration. For breast cancer, the incidence rates in Los Angeles County were also high compared with those in the homelands. However, the timing of immigration to the US was important in determining breast cancer risk. When social security numbers indicated that migration occurred later in life, rates for breast cancer were substantially lower than when migration occurred early, although they were still much higher than in the homeland populations. These findings suggest that environmental factors in early life rather than in later life are important in the etiology of breast cancer and that later life events can substantially impact the likelihood of developing clinically detectable prostate cancer.
883 citations
TL;DR: The finding that soya products may protect against breast cancer in younger women is of interest since these foods are rich in phyto-oestrogens.
794 citations
TL;DR: To quantify the effect of estrogen replacement therapy on breast cancer risk, a combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies was combined.
Abstract: To quantify the effect of estrogen replacement therapy on breast cancer risk, we combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies. Using this summary dose-response slope, we calculated the proportional increase in risk of breast cancer for each year of estrogen use. For women who experienced any type of menopause, risk did not appear to increase until after at least 5 years of estrogen use. After 15 years of estrogen use, we found a 30% increase in the risk of breast cancer (relative risk, 1.3; 95% confidence interval [CI], 1.2 to 1.6). The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. Among women with a family history of breast cancer, those who had ever used estrogen replacement had a significantly higher risk (3.4; CI, 2.0 to 6.0) than those who had not (1.5; CI, 1.2 to 1.7). (JAMA. 1991;265:1985-1990)
619 citations
TL;DR: Women with suspicious abnormal mammograms exhibited significantly elevated levels of mammography-related anxiety and breast cancer worries that interfered with their moods and functioning, despite the fact that diagnostic work-ups had ruled out breast cancer.
Abstract: Evaluated the impact of receiving abnormal mammogram results on women's anxiety and breast cancer worries and on their breast self-examination (BSE) frequency and intentions to obtain subsequent mammograms. A telephone survey was conducted with 308 women 50 years old and older approximately 3 months following a screening mammogram. Subjects included women with suspicious abnormal mammograms, nonsuspicious abnormal mammograms, and normal mammograms. Women with suspicious abnormal mammograms exhibited significantly elevated levels of mammography-related anxiety and breast cancer worries that interfered with their moods and functioning, despite the fact that diagnostic work-ups had ruled out breast cancer. Women with moderate levels of impairment in mood or functioning were more likely to practice monthly BSE than women with either high or low levels of impairment. Breast cancer worries, perceived susceptibility to breast cancer, and physician encouragement to get mammograms all exhibited independent positive relationships to mammogram intentions.
575 citations
TL;DR: 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications.
529 citations
TL;DR: Findings suggest that the chromosomal region 17q12-q23, previously shown to contain a gene for early-onset breast cancer, is also associated with a proportion of hereditary ovarian cancers.
486 citations
TL;DR: It is concluded that radiation pneumonitis following conservative surgery and radiation therapy for breast cancer is a rare complication, and that it is more likely to occur in patients treated with both a 3-field technique and chemotherapy (particularly given concurrently with radiation therapy).
Abstract: The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, we retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone ( n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region ( n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocenter from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (1517, 88%), fever (917,53%), and/or dyspnea (617,35%) and radiographic changes (1717) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1–12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients ( p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (892) compared with 1.3% (3236) for those who received sequential chemotherapy and radiation therapy ( p = 0.002). A casexontrol analysis was performed to determine if the volume of lung irradiated (as determined using central lung distance [CLD]) was related to the risk of developing radiation pneumonitis. Three control patients were matched to each case of radiation pneumonitis based on age, side of lesion, chemotherapy (including sequencing), use of a third field, and year treated. Lung volumes were similar in the radiation pneumonitis cases and controls. We conclude that radiation pneumonitis following conservative surgery and radiation therapy for breast cancer is a rare complication, and that it is more likely to occur in patients treated with both a 3-field technique and chemotherapy (particularly given concurrently with radiation therapy). Over the limited range of volumes treated, lung volume was not associated with an increased risk of radiation pneumonitis.
Journal Article•
TL;DR: Production of PTHrP as a bone-resorbing agent may contribute to the ability of breast cancers to grow as bone metastases.
Abstract: Parathyroid hormone-related protein (PTHrP) has recently been identified in 60% of a series of primary breast cancers. The detection of a bone-resorbing factor in tumors with a propensity to metastasize to bone prompted study of PTHrP in breast cancer metastasis. PTHrP was localized by immunohistology in 12 of 13 (92%) breast cancer metastases in bone and in 3 of 18 (17%) metastases in non-bone sites. The statistical difference was highly significant (P less than 0.0001). Production of PTHrP as a bone-resorbing agent may contribute to the ability of breast cancers to grow as bone metastases.
TL;DR: The study of LN and studies performed by others support the higher risk of IBC after histologically flagrant examples (LCIS, about nine times higher) and a relatively lower but definable risk after more histologically subtle examples (atypical lobular hyperplasia, four to five times lower).
TL;DR: The combination of chemotherapy and tamoxifen was associated with more venous and arterial thromboembolic complications than chemotherapy alone in premenopausal patients and with moreVenous thrombi than tamoxIFen alone among post menopausal patients.
Abstract: The records of 2,673 patients randomized according to seven consecutive Eastern Cooperative Oncology Group (ECOG) studies of adjuvant therapy for breast cancer were reviewed for the occurrence of vascular complications. All protocols opened and closed between June 1977 and July 1987. The objectives of the present study were (1) to compare the frequency of vascular complications among patients who received adjuvant therapy for breast cancer with patients on observation, and (2) to estimate the contribution of chemotherapy and hormonal therapy to the occurrence of venous and arterial thrombi. The frequency of thrombosis, both venous and arterial combined, was 5.4% among patients who received adjuvant therapy and was 1.6% among patients on observation (P = .0002). Premenopausal patients who received chemotherapy and tamoxifen had significantly more venous complications than those who received chemotherapy without tamoxifen (2.8% v 0.8%, P = .03). Postmenopausal patients who received tamoxifen and chemotherapy had significantly more venous thrombi than those who received tamoxifen alone (8.0% v 2.3%, P = .03) or those who were observed (8.0% v 0.4%, P less than .0001). Premenopausal patients who received tamoxifen and chemotherapy had a 1.6% frequency of arterial thrombosis, significantly more than patients who received chemotherapy alone (1.6% v 0.0%, P = .004). The frequency of arterial thrombosis among postmenopausal patients was not significantly correlated with adjuvant therapy. In conclusion, patients who received adjuvant therapy for breast cancer had a 5.4% frequency of thromboembolic complications, significantly more than those who were observed. The combination of chemotherapy and tamoxifen was associated with more venous and arterial thromboembolic complications than chemotherapy alone in premenopausal patients and with more venous thrombi than tamoxifen alone among postmenopausal patients.
TL;DR: Tamoxifen given for at least five years as adjuvant therapy for breast cancer seems to have a cardioprotective oestrogen-like effect in postmenopausal women.
Abstract: OBJECTIVE--To investigate the incidence of fatal myocardial infarction in women in the two randomised arms of the Scottish adjuvant tamoxifen trial. DESIGN--Retrospective review of hospital notes to determine with the greatest possible certainty women who had died of an acute myocardial infarction. SETTING--Scottish Cancer Trials Office, the University of Edinburgh. PATIENTS--1070 postmenopausal women with operable breast cancer who were randomised to receive either adjuvant tamoxifen for five years or until relapse (539 patients) or tamoxifen for at least six weeks on the confirmation of first recurrence (531 patients). MAIN OUTCOME MEASURES--Incidence of fatal myocardial infarction in women with no known or suspected systemic cancer. RESULTS--Of the 200 women who died in the adjuvant tamoxifen arm of the trial, 44 were free of cancer at death and 10 of these died of myocardial infarction. In the observation arm 251 women died, of whom 61 showed no evidence of systemic cancer and 25 had a fatal myocardial infarction. The incidence of fatal myocardial infarction in the two groups was significantly different (chi 2 = 6.88, p = 0.0087). CONCLUSION--Tamoxifen given for at least five years as adjuvant therapy for breast cancer seems to have a cardioprotective oestrogen-like effect in postmenopausal women.
TL;DR: The presence of anti‐Ri antibody identifies a subset of patients with paraneoplastic ataxia and eye movement disorders (opsoclonus) who usually suffer from breast or other gynecological cancer; the antibody when present is a useful marker for an underlying malignancy.
Abstract: The serum and cerebrospinal fluid (CSF) of 8 women with ataxia, 6 of whom also had eye movement abnormalities believed to be opsoclonus, were found to contain a highly specific antineuronal antibody we call anti-Ri. Seven of the 8 women also had or developed cancer: carcinoma of the breast in 5, adenocarcinoma in an axillary lymph node in 1, and carcinoma of the fallopian tube in 1. Four patients presented with the neurological disorder; the cancer was diagnosed first in the other 4. Immunohistochemical studies using serum or CSF from all 8 patients revealed a highly specific antibody interaction with central nervous system neuronal nuclei but not with glial or other cells; the titer ranged from 1:5,000 to 1:320,000 in serum and from 1:2,000 to 1:16,000 in CSF. Biotinylated IgG from the patients' serum reacted with the tumors of 3 of 4 patients with anti-Ri antibody but not with breast cancers from patients without anti-Ri antibody. Immunoblots against cerebral cortex neuronal extracts identified protein antigens of 55-kd and 80-kd relative molecular mass. Serum titers by immunoblot ranged from 1:500 to more than 1:40,000 and CSF titers, from 1:10 to 1:2,000. The relative amount of anti-Ri was always higher in CSF than in serum. The antibody was not present in sera from normal individuals; patients with breast cancer without opsoclonus; other patients with opsoclonus; or patients with other paraneoplastic syndromes related to breast, ovarian, or small-cell lung cancer. We conclude that the presence of anti-Ri antibody identifies a subset of patients with paraneoplastic ataxia and eye movement disorders (opsoclonus) who usually suffer from breast or other gynecological cancer; the antibody when present is a useful marker for an underlying malignancy.
TL;DR: Randomized clinical trials of adjuvant therapy for early-stage breast cancer have demonstrated a 35% decrease in contralateral breast cancers among women receiving tamoxifen compared with controls, suggesting a potential role for tamoxIFen in chemoprevention of breast cancer in women at increased risk of the disease.
Abstract: Despite advances in early detection and treatment of breast cancer, primary prevention has not been well explored, especially for women at increased risk of disease due to reproductive factors and family history. There are, however, suggestions that primary prevention of breast cancer may be a realistic objective. Randomized clinical trials of adjuvant therapy for early-stage breast cancer have demonstrated a 35% decrease in contralateral breast cancers among women receiving tamoxifen compared with controls, suggesting a potential role for tamoxifen in chemoprevention of breast cancer in women at increased risk of the disease. Adjuvant therapy studies also demonstrate that tamoxifen is well tolerated by most patients and suggest additional health benefits from alterations in plasma lipid levels and stabilization of bone mineral loss in women receiving tamoxifen. Aspects of tamoxifen pharmacology, laboratory research, and clinical experience which support its investigation as a chemopreventive agent for breast cancer are summarized, and potential toxic effects are discussed.
TL;DR: The combined results from multiple studies provide strong evidence that menopausal therapy consisting of 0.625 mg/d or less of conjugated estrogens does not increase breast cancer risk.
Abstract: We conducted a meta-analysis of the literature concerning breast cancer and estrogen replacement therapy. The overall relative risk of breast cancer associated with this therapy was 1.07. However, the variation of the estimated risks among the studies was far greater than could plausibly be explained by chance alone. To explain this variation, we looked at the effects of type, duration, and dosage of treatment. Overall, women who took 0.625 mg/d or less of conjugated estrogens had a risk of breast cancer that was 1.08 times that of women who did not receive this therapy (95% confidence interval [CI], 0.96 to 1.2). The relative risks from these individual studies of low-dosage therapy did not differ significantly from each other. Women who took 1.25 mg/d or more of conjugated estrogens had a breast cancer relative risk of 2.0 or less in all studies. However, the variation in observed risks at this higher dosage was significant. This implies that other risk factors varied among these studies, making it difficult to estimate the overall risk associated with this dosage. The relative risk of breast cancer associated with estro gen replacement therapy among women with a history of benign breast disease was 1.16 (95% CI, 0.89 to 1.5). The combined results from multiple studies provide strong evidence that meno pausal therapy consisting of 0.625 mg/d or less of conjugated estrogens does not increase breast cancer risk. (Arch Intern Med.1991;151:67-72)
TL;DR: Despite scientific evidence of the equivalent efficacy of BCS with radiation therapy and mastectomy, BCS is not performed on the majority of women with stage I or II breast cancer, and factors are associated with its use that differ from selection criteria outlined by the National Institutes of Health.
Abstract: Objective. —To identify time trends and factors associated with breast-conserving surgery (BCS) and delivery of postoperative radiation therapy among women with stage I or II breast cancer. Design. ——Survey. Setting. —Population-based cancer registry in the Seattle—Puget Sound (Wash) region. Participants. —The study included 8095 women diagnosed with stage I or II breast cancer (American Joint Committee on Cancer staging criteria) from 1983 through 1989. Main Outcome Measures. —Breast-conserving surgery with or without radiation therapy vs mastectomy, and, among women with BCS, a comparison of radiation therapy vs no therapy. Results. —In 1985 when results from a US randomized clinical trial of BCS were published, the frequency of BCS peaked (46.3% of stage I; 30.1% of stage II) followed by a return to levels before 1985 for women with stage II breast cancer and a more moderate decline for stage I breast cancer. The likelihood of BCS decreased with increasing age ( P P P P Conclusions. —Despite scientific evidence of the equivalent efficacy of BCS with radiation therapy and mastectomy, BCS is not performed on the majority of women with stage I or II breast cancer as recommended by the National Institutes of Health, and factors are associated with its use that differ from selection criteria outlined by the National Institutes of Health. ( JAMA . 1991;266:3433-3438)
TL;DR: Long-term therapy with mifepristone is a new therapeutic option that may have efficacy in cases of unresectable benign meningioma and has shown signs of objective response and subjective improvement in five patients.
Abstract: ✓ The possibility that meningioma growth may be related to female sex hormone levels is suggested by several lines of evidence. Meningiomas are twice as common in women as in men, have been observed to wax and wane with pregnancy, and are positively associated with breast cancer. A physiological explanation for these phenomena is provided by the finding of steroid hormone receptors in meningiomas. However, unlike breast cancer, meningiomas are much more commonly positive for progesterone receptors than for estrogen receptors. The authors initiated a study on long-term oral therapy of unresectable meningiomas with the antiprogesterone mifepristone (RU486). Fourteen patients received mifepristone in daily doses of 200 mg for periods ranging from 2 to 31+ months (≥ 6 months in 12 patients). Five patients have shown signs of objective response (reduced tumor measurement on computerized tomography scan or magnetic resonance image, or improved visual field examination). Three have also experienced subjective im...
TL;DR: The findings suggest that the prognostic value of c‐erbB‐2 over‐expression may be related not only to increased cell proliferation rate but also to a distinctive pattern of metastasis.
Abstract: c-erbB-2 protein over-expression was studied immunohistochemically in 319 paraffin-embedded breast carcinomas representing 89% of all breast-cancer cases operated in the Tampere University Hospital between 1977 and 1981. The immunohistochemical evaluation of c-erbB-2 was optimized using protease pre-treatment and verified using antibodies for both the external and the internal domains of the protein. c-erbB-2 over-expression was found in 72 (23%) of the 319 cases and was associated with high histological and nuclear grade (p less than 0.0001), DNA aneuploidy (p = 0.003), high tumor S-phase fraction (p less than 0.0001), and lack of estrogen (p less than 0.0001) and progesterone (p = 0.03) receptors. Overall, breast-cancer patients with c-erbB-2 over-expression had about 2.2-fold relative risk (RR) of death (p less than 0.001) as compared with those without over-expression. According to a multivariate analysis, c-erbB-2 over-expression was an independent prognostic factor in the whole material as well as in the node-negative sub-set. In node-negative breast-cancer tumor size, S-phase and c-erbB-2 status defined a large patient group with only 4% 5-year and 15% 10-year mortality rate without adjuvant therapy. In comparison with c-erbB-2-negative tumors, those with over-expression of this gene metastasized 3 times more often (p = 0.0002) to the lungs, liver and brain and 3 times less often to the bone. Our findings suggest that the prognostic value of c-erbB-2 over-expression may be related not only to increased cell proliferation rate but also to a distinctive pattern of metastasis.
TL;DR: In this article, the authors present risk factors for breast cancer generally regarded as established, together with their approximate relative risks, including age, country of birth, and a history of breast cancer in both a mother and a sister.
Abstract: Table 5 presents risk factors for breast cancer generally regarded as established, together with their approximate relative risks. With the exception of age, country of birth, and a history of breast cancer in both a mother and a sister, all of the relative risks reported to date are of a relatively modest magnitude. Thus, new risk factors need to be identified and knowledge of existing risk factors refined. Factors for which the evidence of an etiologic role has mounted over the past several years, but which are not yet considered to be established, include the protective effects of parity and lactation in certain age groups and the increased risks associated with alcohol consumption and with DES exposure during pregnancy. In addition, physical activity has emerged as a factor worthy of further study. Some evidence suggests that use of oral contraceptives for several years at an early age modestly increases the risk for breast cancer diagnosed before age 35 and perhaps age 45. Use of estrogen-replacement therapy for 20 years or more has been found by a few studies to increase the risk for breast cancer in the postmenopausal years; further studies of very long-term users are needed. Also, other risks and benefits of these hormones need to be taken into account when women decide whether to use them. Surprisingly elusive has been the etiologic role of endogenous hormones, especially in view of the large number of studies that have been concerned with them. A better understanding of the role of endogenous hormones should help explain the mechanisms of action of known and suspected risk factors. Areas of high priority for further research thus include establishing with more certainty whether the risk for breast cancer is increased in any subgroups of women who use oral contraceptives and estrogen-replacement therapy and determining the etiologic roles of specific endogenous hormones. The possible risks associated with alcohol consumption and lack of physical activity need to be studied more thoroughly, and ideas about new potential risk factors are needed. Although epidemiologic studies will continue to be concerned with diet, enthusiasm for its etiologic role in women has been considerably dampened by the lack of association in many of the studies reported to date. The studies in women exposed to radiation, DES, and oral contraceptives suggest that the timing of some exposures may be critical, since the effects of these agents may mostly be limited to specific time periods of rapid breast development.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: There was an increased risk of relapse and death associated with c-erbB-2 expression irrespective of nodal involvement and this marker thus appears to be a significant prognostic factor in the early as well as the late stages of breast cancer.
Abstract: The c-erbB-2 gene is overexpressed in about 20% of human breast cancers. Four hundred and eighty-three cases previously examined by immunohistochemical staining for c-erbB-2 expression were analysed to assess the risk associated with the elevated protein expression. Oncoprotein expression was correlated with increasing tumour grade but not with oestrogen receptor status, nodal involvement, tumour size or age. There was an increased risk of relapse and death associated with c-erbB-2 expression irrespective of nodal involvement. This marker thus appears to be a significant prognostic factor in the early as well as the late stages of breast cancer.
TL;DR: There is no solid proof of a better psychologic adjustment after breast-conserving treatment and that there are no substantial differences between the different treatment modalities in changes of life patterns and fears and concerns, but the results with respect to body image and sexual functioning favor the use of breast- Conserving treatment.
Abstract: In recent years, doubt has been shed on the necessity of mastectomy for women with early-stage breast cancer. Apart from purely medical studies comparing (radical) mastectomy to less intruding surgical treatment, a number of studies (N = 18) have been published investigating the impact of breast-conserving treatment versus mastectomy on quality of life. We review these studies with respect to medical issues (treatment modality, stage of disease), methodologic issues (design, measurement moment, sample size), and results (psychologic discomfort, changes in life patterns, fears and concerns). It is concluded that there is no solid proof of a better psychologic adjustment after breast-conserving treatment and that there are no substantial differences between the different treatment modalities in changes of life patterns and fears and concerns. However, the results with respect to body image and sexual functioning favor the use of breast-conserving treatment.
TL;DR: In the present issue of this journal, Thor and colleagues attempt to evaluate heat shock protein 27 (also known as the 27 000-dalton stress response protein or srp-27) measured in tumors from breast cancer patients as a prognostic factor, but state that a multivariate analysis failed to recognize srP-27 expression as a significant independent predictive factor.
Abstract: In the present issue of this journal, Thor and colleagues attempt to evaluate heat shock protein 27 (also known as the 27 000-dalton stress response protein or srp-27) measured in tumors from breast cancer patients as a prognostic factor (1). They report significant correlations between srp-27 overexpression and other measured prognostic factors as well as between srp-27 overexpression and a shorter disease-free survival period. However, they state that a multivariate analysis failed to recognize srp-27 expression as a significant independent predictive factor. Before commenting on the Thor paper, it might be useful to consider first the broader problem of how the casual reader should evaluate papers dealing with prognostic factors in breast cancer. The use of prognostic factors to help select breast cancer patients for adjuvant therapy is of considerable concern to the oncology community (2). This need for selection of prognostically less favorable cases is stimulating investigators to identify new and more powerful prognostic factors. Unfortunately, however, this identification process is becoming more confusing because of a lack of guidelines for investigators to use to study new factors and for reviewers and readers to use to evaluate papers on this topic. Listed here are the minimal criteria that must be considered when one is attempting to evaluate a new prognostic factor.
TL;DR: The data suggest that the breast is one of the most sensitive tissues to the carcinogenic force of radiation, that fractionated exposures are similar to single exposures of the same total dose in their ability to induce breast cancer, that risk remains high for many years after exposure, and that young women are especially vulnerable to radiation injury.
Abstract: The incidence of breast cancer was determined in 4940 women treated for tuberculosis between 1925 and 1954 in Massachusetts. Among 2573 women examined by X-ray fluoroscopy an average of 88 times during lung collapse therapy and followed for an average of 30 years, 147 breast cancers occurred in contrast to 113.6 expected [observed/expected (O/E) = 1.29; 95% confidence interval (CI) = 1.1-1.5]. No excess of breast cancer was seen among 2367 women treated by other means: 87 observed versus 100.9 expected. Increased rates for breast cancer were not apparent until about 10 to 15 years after the initial fluoroscopy examination. Excess risk then remained high throughout all intervals of follow-up, up to 50 years after first exposure. Age at exposure strongly influenced the risk of radiation-induced breast cancer with young women being at highest risk and those over age 40 being at lowest risk [relative risk (RR) = 1.06]. Mean radiation dose to the breast was estimated to be 79 cGy, and there was strong evidence for a linear relationship between dose and breast cancer risk. Allowing for a 10-year minimum latent period, the relative risk at 1 Gy was estimated as 1.61 and the absolute excess as 10.7 per 10(4) woman-years per gray. When compared to other studies, our data suggest that the breast is one of the most sensitive tissues to the carcinogenic force of radiation, that fractionated exposures are similar to single exposures of the same total dose in their ability to induce breast cancer, that risk remains high for many years after exposure, and that young women are especially vulnerable to radiation injury.
TL;DR: Mitoxantrone is an effective and better tolerated alternative to the anthracyclines in most haematological malignancies, in breast cancer and in advanced hepatic or ovarian carcinoma, and synergy with other antineoplastic drugs has been demonstrated in murine tumour models.
Abstract: Mitoxantrone is a dihydroxyanthracenedione derivative which as intravenous mono- and combination therapy has demonstrated therapeutic efficacy similar to that of standard induction and salvage treatment regimens in advanced breast cancer, non-Hodgkin's lymphoma, acute nonlymphoblastic leukaemia and chronic myelogenous leukaemia in blast crisis; it appears to be an effective alternative to the anthracycline component of standard treatment regimens in these indications. Mitoxantrone is also effective as a component of predominantly palliative treatment regimens for hepatic and advanced ovarian carcinoma. Limited studies suggest useful therapeutic activity in multiple myeloma and acute lymphoblastic leukaemia. Regional therapy of malignant effusions, hepatic and ovarian carcinomas has also been very effective, with a reduction in systemic adverse effects. Mitoxantrone inhibits DNA synthesis by intercalating DNA, inducing DNA strand breaks, and causing DNA aggregation and compaction, and delays cell cycle progression, particularly in late S phase. In vitro antitumour activity is concentration- and exposure time-proportional, and synergy with other antineoplastic drugs has been demonstrated in murine tumour models. Leucopenia may be dose-limiting in patients with solid tumours, whereas stomatitis may be dose-limiting in patients with leukaemia. Other adverse effects are usually of mild or moderate severity although cardiac effects, particularly congestive heart failure, may be of concern, especially in patients with a history of anthracycline therapy, mediastinal irradiation or cardiovascular disease. Mitoxantrone displays an improved tolerability profile compared with doxorubicin and other anthracyclines, although myelosuppression may occur more frequently. Thus, mitoxantrone is an effective and better tolerated alternative to the anthracyclines in most haematological malignancies, in breast cancer and in advanced hepatic or ovarian carcinoma. Further studies may consolidate its role in the treatment of these and other malignancies.
TL;DR: The results indicated a highly significant association between scores for the tendency to control emotional reactions and a fatalistic attitude toward cancer, and a significant association was observed between anger control and a helpless attitude.
Abstract: The possible relationship between psychological responses among breast cancer patients and disease outcome continues to be an area of controversy and debate. Two parallel findings are reported separately in the literature: first, that emotional control is more common among women with breast cancer than in women with benign breast disease or in healthy controls and second, that a helpless attitude towards the disease is related to a poor prognosis. These previously unrelated psychological responses are examined here in a group of women (N = 359) with early stage breast cancer, who were seen one to three months after diagnosis. The relationships between emotional control, adjustment to cancer and psychological morbidity were examined. Prevalence levels of 16 and 6% were observed for anxiety and depression respectively, which are lower than reported more generally in the literature. The results indicated a highly significant association between scores for the tendency to control emotional reactions and a fatalistic attitude toward cancer. A significant association was observed between anger control and a helpless attitude. Psychological morbidity was also linked to type of adjustment to cancer. The data are interpreted in terms of a process model of psychological responses which suggests that emotional control (an important component of the Type C behaviour pattern) fatalism, helplessness and psychological morbidity are linked.
Journal Article•
TL;DR: The data strongly suggest that amplification of c-erbB-2 may contribute to the pathogenesis of some forms of node-negative breast cancer and thus may serve as a useful genetic marker to identify a subset of high-risk patients.
Abstract: Drawing upon the comprehensive population-based Northern Alberta Breast Cancer Registry containing 704 patients with histologically negative axillary lymph nodes who have been followed for 5-16 years, we have undertaken a retrospective case-control study to evaluate the utility of genomic amplification of specific protooncogenes [c-erbB-2 (nee HER-2/neu), c-erbA, c-myc, int-2, and hst-1] as predictive indicators of clinical outcome in node-negative disease. To this end, 115 women with node-negative breast cancer who had recurred at any time up to 16 years posttreatment (cases) were matched pairwise for appropriate clinicopathological variables (size of primary tumor, menopausal state, estrogen receptor status, anniversary year of treatment, and patient age) with a second group of 115 women (controls) selected from a cohort of 502 node-negative patients who had not relapsed during long-term follow-up. Tumor DNA extracted from archival formalin-fixed, paraffin-embedded tissue blocks were analyzed for protooncogene copy number by slot-blot hybridization. Taking a gene copy number of 3 as the cutoff, 27 of the 230 tumor samples examined contained from 3- to 22-fold elevation in c-erbB-2 genomic equivalents. Twenty-one of the 27 tumors amplified for c-erbB-2 were derived from cases and 6 from controls, signifying that 18% of the node-negative patients who had relapsed harbored excessive copies of the protooncogene in their malignant tissue compared to only 5% for the patients who had remained in remission. Accordingly, the occurrence of amplification of c-erbB-2 proved to be a statistically significant predictor of poor prognosis, especially disease-free interval (P = 0.006). Moreover, this genetic alteration appeared to be independent of and to have greater predictive power than most commonly used prognostic factors. Our findings also indicated that as a clinical test, measurement of c-erbB-2 amplification suffers from low sensitivity; however, when greater than 6 gene copies are present, the test has a positive predictive value for recurrence of 70%. Concurrent analysis of tumor DNA blots with probes for the other four protooncogenes examined revealed that their amplification, which others have reported to arise often, especially in node-positive disease, was seldom found even in our high-risk case group (2-3%). In short, our data strongly suggest that amplification of c-erbB-2 may contribute to the pathogenesis of some forms of node-negative breast cancer and thus may serve as a useful genetic marker to identify a subset of high-risk patients.
TL;DR: It is suggested that the percentage of mammographic densities in the breast can predict breast cancer risk more accurately than a qualitative assessment of mammography patterns.
Abstract: To determine the relation of mammographic densities to subsequent breast cancer risk, a case-control study was undertaken using prediagnostic mammograms of screening program participants. Mammograms of cases (n = 266) and controls (n = 301) were blindly assessed for mammographic densities, which were measured by planimetry. The odds of breast cancer increased steadily with increasing breast density (test for trend, P less than 0.0001). Breast cancer odds was 1.7 for densities between 5% and 24.9%, 2.5 for 25% through 44.9%, 3.8 for 45% through 64%, and 4.3 for densities of 65% and greater (referent = less than 5% densities). Odds ratios also increased with increasing densities among women with the P2 and DY mammographic patterns. These findings suggest that the percentage of mammographic densities in the breast can predict breast cancer risk more accurately than a qualitative assessment of mammographic patterns.