Showing papers on "Breast cancer published in 1985"
TL;DR: It is concluded that segmental mastectomy, followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for Stage I and II breast tumors less than or equal to 4 cm, provided that margins of resected specimens are free of tumor.
Abstract: In 1976 we began a randomized trial to evaluate breast conservation by a segmental mastectomy in the treatment of Stage I and II breast tumors less than or equal to 4 cm in size. The operation removes only sufficient tissue to ensure that margins of resected specimens are free of tumor. Women were randomly assigned to total mastectomy, segmental mastectomy alone, or segmental mastectomy followed by breast irradiation. All patients had axillary dissections, and patients with positive nodes received chemotherapy. Life-table estimates based on data from 1843 women indicated that treatment by segmental mastectomy, with or without breast irradiation, resulted in disease-free, distant-disease-free, and overall survival at five years that was no worse than that after total breast removal. In fact, disease-free survival after segmental mastectomy plus radiation was better than disease-free survival after total mastectomy (P = 0.04), and overall survival after segmental mastectomy, with or without radiation, was better than overall survival after total mastectomy (P = 0.07, and 0.06, respectively). A total of 92.3 per cent of women treated with radiation remained free of breast tumor at five years, as compared with 72.1 per cent of those receiving no radiation (P less than 0.001). Among patients with positive nodes 97.9 per cent of women treated with radiation and 63.8 per cent of those receiving no radiation remained tumor-free (P less than 0.001), although both groups received chemotherapy. We conclude that segmental mastectomy, followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for Stage I and II breast tumors less than or equal to 4 cm, provided that margins of resected specimens are free of tumor.
2,044 citations
TL;DR: It is demonstrated that the majority of women who undergo breast biopsy for benign disease are not at increased risk of cancer, however, patients with a clinically meaningful elevation in cancer risk can be identified on the basis of atypical hyperplasia and a family history of breast cancer.
Abstract: To assess the importance of various risk factors for breast cancer in women with benign proliferative breast lesions, we reevaluated 10,366 consecutive breast biopsies performed in women who had presented at three Nashville hospitals. The median duration of follow-up was 17 years for 3303 women, 1925 of whom had proliferative disease. This sample contained 84.4 per cent of the patients originally selected for follow-up. Women having proliferative disease without atypical hyperplasia had a risk of cancer that was 1.9 times the risk in women with nonproliferative lesions (95 per cent confidence interval, 1.2 to 2.9). The risk in women with atypical hyperplasia (atypia) was 5.3 times that in women with nonproliferative lesions (95 per cent confidence interval, 3.1 to 8.8). A family history of breast cancer had little effect on the risk in women with nonproliferative lesions. However, the risk in women with atypia and a family history of breast cancer was 11 times that in women who had nonproliferative lesions without a family history (95 per cent confidence interval, 5.5 to 24). Calcification elevated the cancer risk in patients with proliferative disease. Although cysts alone did not substantially elevate the risk, women with both cysts and a family history of breast cancer had a risk 2.7 times higher than that for women without either of these risk factors (95 per cent confidence interval, 1.5 to 4.6). This study demonstrates that the majority of women (70 per cent) who undergo breast biopsy for benign disease are not at increased risk of cancer. However, patients with a clinically meaningful elevation in cancer risk can be identified on the basis of atypical hyperplasia and a family history of breast cancer.
1,710 citations
TL;DR: 7 years after the start of the study the excess of stage I cancers in the study group largely outweighs the deficit of advanced cancers, and the results to the end of 1984 show a 31% reduction in mortality from breast cancer and a 25% reduced in the rate of stage II or more advanced breast cancers.
1,696 citations
TL;DR: It is indicated that the location of a breast tumor does not influence the prognosis and that irradiation of internal mammary nodes in patients with inner-quadrant lesions does not improve survival and that the results obtained at five years accurately predict the outcome at 10 years.
Abstract: In 1971 we began a randomized trial to compare alternative local and regional treatments of breast cancer, all of which employ breast removal. Life-table estimates were obtained for 1665 women enrolled in the study for a mean of 126 months. There were no significant differences among three groups of patients with clinically negative axillary nodes, with respect to disease-free survival, distant-disease--free survival, or overall survival (about 57 per cent) at 10 years. The patients were treated by radical mastectomy, total ("simple") mastectomy without axillary dissection but with regional irradiation, or total mastectomy without irradiation plus axillary dissection only if nodes were subsequently positive. Similarly, no differences were observed between patients with clinically positive nodes treated by radical mastectomy or by total mastectomy without axillary dissection but with regional irradiation. Survival at 10 years was about 38 per cent in both groups. Our findings indicate that the location of a breast tumor does not influence the prognosis and that irradiation of internal mammary nodes in patients with inner-quadrant lesions does not improve survival. The data also demonstrate that the results obtained at five years accurately predict the outcome at 10 years. We conclude that the variations of local and regional treatment used in this study are not important in determining survival of patients with breast cancer.
1,278 citations
TL;DR: The expected rates of local recurrences after breast‐conserving surgical procedures relative to the extensiveness of the excision are estimated and the possible impact of postoperative local radiation therapy on the rates of expected local recurrence is discussed.
Abstract: Breast cancer multifocality was studied in mastectomy specimens by correlated specimen radiography and histologic techniques. The patients chosen for study were comparable to those eligible for breast-conserving surgical therapy. Two study groups, one with 282 invasive cancers (T1-2) and the other with 32 intraductal cancers, were selected from a group of 399 consecutive cases by omitting patients who were clearly, or very probably, not candidates for breast-conserving surgical therapy according to current trial criteria. Omitted patients included those with clinically and/or radiologically multifocal cancers and patients with tumor extension into the chest wall or skin (7%). Also excluded were the so-called diffuse invasive cancers (8%), the clinically and radiologically occult tumors (3%), and the invasive cancers larger than 5 cm (3%). Of the 282 invasive cancers, 105 (37%) showed no tumor foci in the mastectomy specimen around the reference mass. In 56 (20%) tumor foci were present within 2 cm, and in 121 (43%) tumor was found more than 2 cm from the reference tumor. In 75 (27%) the tumor foci beyond 2 cm were histologically noninvasive cancers, and in 46 cases (16%) they contained invasive cancers as well. A comparison between the group with reference tumors less than 2 cm and the group with reference tumors more than 2 cm in size showed no significant difference between the groups in terms of presence or absence of tumor foci or distance of tumor foci from the reference tumor. If the 264 invasive cancers in this series that were 4 cm or less in diameter had been removed with a margin of 3 to 4 cm, 7% to 9% of the patients would have had invasive cancer left in the remaining breast tissue, and 4% to 9% would have had foci of noninvasive cancer left in the remaining breast tissue. On the basis of the data on the distribution of tumor at different distances from the reference tumor, the current study estimates the expected rates of local recurrences after breast-conserving surgical procedures relative to the extensiveness of the excision. The possible impact of postoperative local radiation therapy on the rates of expected local recurrence is discussed.
1,088 citations
TL;DR: The authors conclude that among the epithelial hyperplastic lesions of the human breast, a minority may be recognized by their resemblance to CIS which have a clinically significant elevation of subsequent breast cancer risk.
Abstract: A total of 10,542 breast biopsy specimens obtained between 1950 and 1968 were studied. Examples of atypical "ductal" (ADH) and atypical lobular hyperplasia (ALH), defined as having only some features of carcinoma in situ (CIS), were diagnosed in 3.6% of these specimens. In the same series, CIS was diagnosed in 1.7% of biopsy specimens excluding those with invasive cancer. The subsequent risk of invasive breast carcinoma after ALH or ADH was 4-5 times that of the general population. Follow-up was 90% successful and extended 17 years after biopsy. History of breast cancer in a mother, sister, or daughter doubled the risk of subsequent invasive carcinoma development (to 8 times for ALH and 10 times for ADH). The authors conclude that among the epithelial hyperplastic lesions of the human breast, a minority may be recognized by their resemblance to CIS which have a clinically significant elevation of subsequent breast cancer risk. This risk is one-half that of CIS.
894 citations
TL;DR: It is observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.
Abstract: Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and a low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.
409 citations
TL;DR: Analysis of cellular DNA content of paraffin-embedded histological material from cancer patients shows a generally more favorable prognosis for patients with diploid tumors, except in the presence of recurrent or metastatic disease.
Abstract: By using a recently developed flow cytometric method we have analyzed cellular DNA content of paraffin-embedded histological material from cancer patients. This method allows the retrospective study of tumors from patients whose clinical outcome is already known, and we have applied it to ovarian cancers, stage II breast cancers, and to metastatic adenocarcinoma of unknown primary site. In addition to knowledge of patient survival, comprehensive information was available about other prognostic determinants and treatment received, and we have used multivariate analysis in an attempt to determine the prognostic significance of cellular DNA content. In ovarian cancer, it is a major prognostic variable except in stage IV disease, whereas in metastatic adenocarcinoma of unknown primary site cellular DNA content has no influence on survival. For stage II breast cancer the situation is more complex and requires larger numbers to be studied. However, aneuploid tumors tend to have more extensive involvement of axillary lymph nodes and a poorer overall disease-free survival. This influence of DNA content on disease-free survival appears to be confined to premenopausal patients, and has no effect on patient survival following disease recurrence. Although we need to study more patients and more turnor types, taken together the results so far show a generally more favorable prognosis for patients with diploid tumors, except in the presence of recurrent or metastatic disease. The better prognosis associated with diploid tumors could be due to the fact that they are more commonly found in earlier clinical stages rather than to their being inherently less aggressive than aneuploid tumors.
397 citations
TL;DR: Women who were under 30 or over 50 years of age when irradiated were at greatest absolute risk for developing a second cancer, and the RR was higher among those under age 30 years at exposure than among older women.
Abstract: The numbers of second cancers among 182,040 women treated for cervical cancer that were reported to 15 cancer registries in 8 countries were compared to the numbers expected had the same risk prevailed as in the general population. A small 9% excess of second cancers (5,146 observed vs. 4,736 expected) occurred 1 or more years after treatment. Large radiation doses experienced by 82,616 women did not dramatically alter their risk of developing a second cancer; at most, about 162 of 3,324 second cancers (approximately equal to 5%) could be attributed to radiation. The relative risk (RR = 1.1) for developing cancer in organs close to the cervix that had received high radiation exposures--most notably, the bladder, rectum, uterine corpus, ovary, small intestine, bone, and connective tissue--and for developing multiple myeloma increased with time since treatment. No similar increase was seen for 99,424 women not treated with radiation. Only a slight excess of acute and non-lymphocytic leukemia was found among irradiated women (RR = 1.3), and substantially fewer cases were observed than expected on the basis of current radiation risk estimates. The small risk of leukemia may be associated with low doses of radiation absorbed by the bone marrow outside the pelvis, inasmuch as the marrow in the pelvis may have been destroyed or rendered inactive by very large radiotherapy exposures. There was little evidence of a radiation effect for cancers of the stomach, colon, liver, and gallbladder, for melanoma and other skin cancers, or for chronic lymphocytic leukemia despite substantial exposures. An excess of thyroid cancer possibly was related to the low dose received by this organ. Ovarian damage caused by radiation may have been responsible for a low breast cancer risk (RR = 0.7), which was evident even among postmenopausal women. A substantial excess of lung cancer (RR = 3.7) largely may be due to misclassification of metastases and the confounding influence of cigarette smoking. Women who were under 30 or over 50 years of age when irradiated were at greatest absolute risk for developing a second cancer. The RR, however, was higher among those under age 30 years at exposure (RR = 3.9) than among older women. The expression period for radiation-induced solid tumors appeared to continue to the end of life.
343 citations
TL;DR: Information on the presence or absence of internal mammary node metastases would be of great importance in formulating the prognosis of breast cancer patients and a biopsy at the first intercostal space may be reasonable in selected patients as long as noninvasive methods of diagnosis are available.
Abstract: The results of the analysis carried out on data on 1119 patients with operable breast cancer treated at the National Cancer Institute of Milan from 1965 to 1979 with enlarged mastectomy are reported. Metastases to internal mammary chain were found to be significantly associated with the maximum diameter of primary (16.1% for tumors less than 2 cm and 24.5% for larger tumors, p = 0.007), the age of the patients (27.6% in patients younger than 40 years, 19.7% in patients between 41-50 years, and 15.6% in patients older than 50 years, p = 0.01). The site of origin of the cancer had no impact on internal mammary node metastases. Patients with positive axillary nodes showed metastases to internal mammary nodes in 29.1% of the cases, while 9.1% of patients with axillary negative nodes had positive retrosternal nodes. Survival was significantly affected by the presence of positive internal mammary nodes: the percentage of 10-year survival varied from 80.4% in patients with axillary and internal mammary negative nodes to 30.0% in patients with both nodal basins involved. Intermediate survival rates (54.6% and 53.0%) were found when one or the other of the nodal stations (axillary and internal mammary) was separately affected. Maximum diameter of the primary significantly affected the survival of each group identified by the status of both axillary and internal mammary nodes. In conclusion, the information on the presence or absence of internal mammary node metastases would be of great importance in formulating the prognosis of breast cancer patients. To obtain this information, a biopsy at the first intercostal space may be reasonable in selected patients (age, maximum diameter, and axillary node involvement being the basis for selection) as long as noninvasive methods of diagnosis are available.
340 citations
TL;DR: In 271 breast cancer patients with adequate follow‐up for at least 5.5 and maximally 12 years, the value of morphometry to classic prognosticators of breast cancer was assessed and it was found that mitotic activity index is the best single predictor of the prognosis.
Abstract: In 271 breast cancer patients with adequate follow-up for at least 5.5 and maximally 12 years, the value of morphometry to classic prognosticators of breast cancer (tumor size and axillary lymph node status) was assessed. Previous studies had indicated the value of this quantitative microscopic technique. Apart from quantitative microscopic features, subjective qualitative features such as nuclear and histologic grade were assessed as well. Univariate life-table analysis showed the significance (p less than 0.001) of several features such as lymph node status, tumor size, nuclear and histologic grade, and several morphometric variables (mitotic activity index, mean and standard deviation of nuclear area). Cellularity index was also significant (p = 0.02). Survival analysis with Cox's regression model, using a stepwise selection as well as backwards elimination, pointed to three features: mitotic activity index, tumor size, and lymph node status. Mitotic activity was the most important prognostic feature, but the combination of these three features in a multivariate prognostic index had even more prognostic significance. Kaplan-Meier curves showed that the 5-year survival of lymph node-negative patients (n = 146) is 85%, versus 93% in patients with a "good prognosis index" (n = 150). For lymph node-positive patients (n = 125), 5-year survival was 55%, compared with 47% in the "high index" (poor prognosis) patients (n = 121). Logistic discriminant analysis with 5.5-year follow-up as a fixed endpoint (191 survivors and 80 nonsurvivors) essentially gave the same results. Application of two instead of one decision threshold (e.g., numerical classification probability 0.60 and 0.40) decrease the number of false-negative and false-positive outcomes, however, with a number of patients falling in the class "uncertain." Thus, in agreement with other studies, morphometry significantly adds to the prognosis prediction of lymph node status and tumor size. Mitotic activity index is the best single predictor of the prognosis. An additional index advantage is that the multivariate model results in a continuous index variable that can be subdivided in many classes with an increasing risk of recurrence, so that more refined clinical therapeutic decision making is possible in individual patient care. The morphometric techniques are inexpensive and fairly simple and therefore can be applied in most pathology laboratories.
TL;DR: The management of IBC appeared to differ from the treatment of other forms of breast cancer; chemotherapy was given more frequently as the first course of cancer-directed therapy in white SEER females with evidence of MO IBC compared with the group with MO non-IBC.
Abstract: The current status of inflammatory breast cancer (IBC) among U.S. females was reviewed with the use of data abstracted from medical records of patients diagnosed with breast cancer between 1975 and 1981 in nine geographic areas covered by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Patients were selected on the basis of reported clinical and pathologic features of IBC and were divided into 3 groups: I) both clinical and pathologic features of IBC; II) clinical features without pathologic confirmation; and III) pathologic evidence only. The age distribution of pathologically defined IBC, in general, showed younger ages than those for other breast cancers in both the white and black populations. Further analysis was restricted to white females due to the relatively small numbers of black and other nonwhite patients with IBC. The disease presentations of both clinically and pathologically defined IBC were similar with regard to the likelihood of the presence of metastases at initial staging. Survival was evaluated by comparison of patients with nonmetastatic (MO) disease. Three years after diagnosis, the relative survival rates among patients in groups I, II, and III were observed to be 34, 60, and 52%, respectively. Survival of patients with all other types of breast cancer was 90% at 3 years. The management of IBC appeared to differ from the treatment of other forms of breast cancer; chemotherapy was given more frequently as the first course of cancer-directed therapy in white SEER females with evidence of MO IBC compared with the group with MO non-IBC. When all possible combinations of initial therapy were considered, the treatment for IBC was more variable than the treatment for non-IBC.
TL;DR: It is concluded that long term athletic training may lower the risk of breast cancer and cancers of the reproductive system.
Abstract: The prevalence (lifetime occurrence) rate of cancers of the reproductive system (uterus, ovary, cervix and vagina) and breast cancer was determined for 5,398 living alumnae, 2,622 of whom were former college athletes and 2,776 non-athletes, from data on medical and reproductive history, athletic training and diet. The former athletes had a significantly lower risk of cancer of the breast and reproductive system than did the non-athletes. The relative risk (RR), non-athletes/athletes, for cancers of the reproductive system was 2.53. 95% confidence limits (CL) (1.17, 5.47). The RR for breast cancer was 1.86, 95% CL (1.00, 3.47). The analysis controlled for potential confounding factors including age, family history of cancer, age of menarche, number of pregnancies, use of oral contraceptives, use of oestrogen in the menopausal period, smoking, and leanness. Of the college athletes, 82.4% had been on pre-college teams compared to 24.9% of the college non-athletes. We conclude that long term athletic training may lower the risk of breast cancer and cancers of the reproductive system.
TL;DR: The “estrogen window hypothesis” of the etiology of breast cancer proposes that unopposed estrogen stimulation is the most favorable state for tumor induction and that normal postovulation progesterone secretion reduces susceptibility.
Abstract: The "estrogen window hypothesis" of the etiology of breast cancer proposes that unopposed estrogen stimulation is the most favorable state for tumor induction and that normal postovulation progesterone secretion reduces susceptibility. The authors believe that epidemiologic and experimental studies suggest rather that the opposite is true, i.e., that breast cancer risk is directly related to the cumulative number of regular ovulatory cycles. Unlike the endometrium, breast tissue mitotic activity is enhanced in the luteal phase of the menstrual cycle. Regular vigorous physical activity is one method of reducing the frequency of ovulatory cycles, and such exercise could markedly reduce a woman's lifetime risk of developing breast cancer.
Journal Article•
TL;DR: Women who received initial radiotherapy compared with those who did not were at slightly higher risk of developing a second cancer, most notably acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, and cancers of the esophagus, kidney, and connective tissue, although the nature of the associations was not always clear.
Abstract: Among 41,109 women diagnosed with breast cancer between 1935 and 1982 in Connecticut, 3,984 developed a second cancer, whereas 2,426 were expected [relative risk (RR) = 1.64; 95% CI = 1.6-1.7]. This increased risk persisted for 30 years and was highest in women under 55 years of age at the time of breast cancer diagnosis. Second primary breast cancers (RR = 3.0) accounted for almost one-half of all new neoplasms. However, if subsequent breast cancers were excluded, the risk for all other second cancers was only 1.15 (95% CI = 1.10-1.20), and no excess risk was seen among women over age 55 at initial breast cancer. Significant risks were found for cancers of the ovary (RR = 1.7) and uterine corpus (RR = 1.4), possibly linked with shared reproductive factors such as nulliparity or late age at menopause. Malignant melanoma (RR = 1.5), thyroid cancer (RR = 1.6), and colon cancer (RR = 1.2) were also significantly elevated; possible shared risk factors remain to be elucidated. Significant deficits of multiple myeloma and chronic lymphocytic leukemia were noted. Women who received initial radiotherapy compared with those who did not were at slightly higher risk of developing a second cancer, most notably acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, and cancers of the esophagus, kidney, and connective tissue, although the nature of the associations was not always clear. Some of the soft tissue sarcomas were lymphangiosarcomas of the arm, a consequence of the lymphedema that may complicate radical mastectomy (Stewart-Treves syndrome). Women treated with radiation were at higher risk of developing a second breast neoplasm (RR = 3.9) than nonirradiated women (RR = 2.8). Further investigation should focus on the mechanisms underlying the relationships between breast, genital tract, and colon cancers, and on the effects of treatment modalities on the risk of subsequent neoplasms.
TL;DR: It is suggested that 6 cycles of CMF can be considered a simple, safe, and moderately effective adjuvant therapy, and in women at very high risk of early relapse more vigorous drug regimens should be concentrated within the first six months from local-regional therapy.
Abstract: The paper reviews all adjuvant studies carried out since 1973 at the Milan Cancer Institute in women with resectable breast cancer and positive axillary nodes. The updated results essentially confirm previous findings, and indicate that CMF-based chemotherapy is able to exert a prolonged therapeutic activity in a fraction of patients bearing micrometastases. In particular, the first randomized study testing no postoperative chemotherapy vs 12 CMF cycles, showed a 10-year relapse free survival (RFS) of 31.4% vs 43.4% (P<0.001) and an overall survival (OS) of 47.3% vs 55.2% (P = 0.10), respectively. Findings related to subsets indicated that RFS and OS benefit was significant in premenopausal and not in postmenopausal women, and in both treatment groups the observed findings were always related to the number of histologically positive nodes. On relapse, salvage therapy administered to controls failed to produce superior results compared to those achieved in the CMF group. The 8-year results of the second study testing 12 vs 6 CMF cycles failed to show a significant difference between the two treatment groups. This indicated that the maximum tumor cell kill occurred during initial chemotherapy cycles. In the third study, carried out only in postmenopausal women ⩽65 years, sequential non-cross resistant combinations (CMFP → AV) at full dose achieved superior results compared to CMF in the subset with limited nodal extent. Acute side effects were moderate and no delayed morbidity, including increased incidence of second neoplasms, was observed. We conclude that the tumor cell heterogeneity, and in particular primary drug resistance, represents the major obstacle to adjuvant systemic therapy in high risk breast cancer. Current results suggest that 6 cycles of CMF can be considered a simple, safe, and moderately effective adjuvant therapy. Future trials should contemplate treatments of different intensity related to major prognostic subsets, while in women at very high risk of early relapse more vigorous drug regimens should be concentrated within the first six months from local-regional therapy.
TL;DR: The study investigated the predictive power of an immunologic effector cell, the natural killer (NK) cell, as well as selected psychological and demographic factors, to breast cancer prognostic risk status and found that NK activity predicted the status of cancer spread to the axillary lymph nodes.
Abstract: Although findings from recent animal studies suggest that behavioral factors such as "helplessness" play a role in cancer progression, very few such studies with humans have been carried out. The study investigated the predictive power of an immunologic effector cell, the natural killer (NK) cell, as well as selected psychological and demographic factors, to breast cancer prognostic risk status. It was found that NK activity predicted the status of cancer spread to the axillary lymph nodes. Patients who had low levels of NK activity were rated as well-adjusted to their illness; patients who had higher NK activity appeared to be distressed or maladjusted. These findings are discussed in the light of recent animal findings linking environmental stress and behavioral responsiveness to biological vulnerability via endocrine and immune pathways.
TL;DR: There was a significant correlation between the presence of the growth factor receptor and poor prognosis as assessed by the Bloom and Richardson score, suggesting that epidermal growth factor receptors state could be a useful prognostic marker.
Abstract: Epidermal growth factor receptors are present in some breast cancers in man, and there is an inverse relation to oestrogen receptor state. We assessed the presence of epidermal growth factor receptors as a single prognostic indicator in a series of breast tumours by comparing this with the Bloom and Richardson scores for these tumours. One hundred and eight ductal tumours were examined for epidermal growth factor receptors by radioligand binding. There was a significant (p less than 0.01) correlation between the presence of the growth factor receptor and poor prognosis as assessed by the Bloom and Richardson score, suggesting that epidermal growth factor receptor state could be a useful prognostic marker. Epidermal growth factor receptor state was not significantly correlated with the lymph node state but showed a tendency to be associated with large tumours.
TL;DR: The risk of breast cancer for a woman was higher if her first-degree relative had unilateral rather than bilateral breast cancer or had breast cancer detected at a younger rather than older age.
Abstract: To investigate whether a family history of breast cancer increases a woman's risk of developing breast cancer, we analyzed data from the Centers for Disease Control's Cancer and Steroid Hormone Study. The 4,735 cases were women 20 to 54 years old with a first diagnosis of breast cancer ascertained from eight population-based cancer registries; the 4,688 controls were women selected at random from the general population of these eight areas. Compared with women without a family history of breast cancer, women who had an affected first-degree relative had a relative risk of 2.3; women with an affected second-degree relative had a relative risk of 1.5; and women with both an affected mother and sister had a relative risk of 14. The risk of breast cancer for a woman was higher if her first-degree relative had unilateral rather than bilateral breast cancer or had breast cancer detected at a younger rather than older age. For women aged 20 to 39, 40 to 44, and 45 to 54 years, the estimated annual incidence of breast cancer per 100,000 women attributable to a first-degree family history of breast cancer was 51.9, 115.1, and 138.6, respectively, and that attributable to a second-degree family history of breast cancer was 12.1, 19.2, and 92.4, respectively. ( JAMA 1985;253:1908-1913)
TL;DR: The data indicate a continuing, albeit modest, increase in the probabilities of eventually developing cancer in each of the four sex-race groups, both excluding and including carcinoma in situ.
Abstract: The usual measures of the magnitude of the cancer problem are annual incidence and mortality data We present another measure of the magnitude of the cancer problem We computed the probabilities at birth and at various ages of developing or dying of the disease within 10 years, 20 years, or total lifetime and show the trends that have occurred in these data since 1975 These probabilities were computed for males and females and among whites and blacks for 1975 and 1980, and projected to 1985 The data indicate a continuing, albeit modest, increase in the probabilities of eventually developing cancer in each of the four sex-race groups, both excluding and including carcinoma in situ White males now show the highest probability at birth of eventually developing cancer, and black females, the lowest, with the figures for the other two groups being intermediate Larger increases were seen for males between 1980 and 1985 (more than three percent) than for females (two percent or less) A child born in the US in 1985 has more than one in three chances of eventually developing invasive cancer (exclusive of epidermoid skin cancer) By site, for males the largest probabilities and the largest increases in the probabilities are for eventually developing lung and prostate cancer For women, the largest eventual probabilities are for breast cancer, almost one in 10 for white females and one in 14 for black females The largest increases are seen for lung cancer and cancer of the colon-rectum The probability of eventually dying of cancer is increasing among the four sex-race groups and is now greater for males of both races than for their female counterparts For males born in 1985, the chances of eventual death from cancer are almost one in four, and for females, almost one in five With the long-term, downward trends in terms of other causes of death--most specifically, decreases in mortality from cardiovascular diseases--the effect on the population at large is greater longevity This situation, in turn, leaves more people longer time to be exposed to cancer risks Thus, while the probabilities of developing or dying of cancer are seen to increase, the increases should be viewed in light of the increasing numbers of people available for such an occurrence(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: The findings suggest that the apparent excess risk of breast cancer among lean premenopausal women may result at least in part from easier, and thus earlier, diagnosis of less aggressive tumors.
Abstract: Although higher relative weight is generally considered to increase the risk of breast cancer, several case-control studies have suggested that the reverse may be true among premenopausal women The association between Quetelet's index (a measure of relative weight calculated as weight/height) and the subsequent incidence of breast cancer was therefore examined during four years of follow-up among a cohort of 121,964 US women who were 30-55 years of age in 1976 In contrast to women who had experienced natural menopause or bilateral oophorectomy, the incidence of breast cancer among premenopausal women decreased with higher levels of relative weight Age-adjusted relative risks for increasing quintiles of Quetelet's index were 100, 090, 090, 073, and 066 (Mantel extension test for trend = -282, p = 0005) This inverse association was not explained by known risk factors for breast cancer and was somewhat stronger when Quetelet's index was computed using reported weight at age 18 years The excess incidence of breast cancer among lean premenopausal women, however, was limited to tumors that were less than 20 cm in diameter, were not associated with metastases to lymph nodes, and were well-differentiated These findings suggest that the apparent excess risk of breast cancer among lean premenopausal women may result at least in part from easier, and thus earlier, diagnosis of less aggressive tumors
TL;DR: The length of follow-up was positively associated with the relative risk of many cancers, although this finding was not as consistent as that with age.
Abstract: The material of the Finnish Cancer Registry from 1953-79 (279,745 cancer patients, 774,518 person-yr at risk) was analyzed for the occurrence of multiple cancer. There were 5,871 new primary cancers in the series (excluding the first 12 mo from diagnosis of the first cancer). A positive association between cancers with similar etiology could be demonstrated, e.g., between cancers of the lip, larynx, and lung (smoking) and between cancers of the breast and endometrium (hormones, reproductive history). Clustering of different risk factors resulted, e.g., in an excess risk of colon cancer among female breast cancer patients (risk factors in both cancers are prevalent particularly in higher-social classes). Differences in the distribution of the risk factors resulted in risk deficits, e.g., low relative risk of lung cancer among male colon cancer patients (the prevalence of smoking was highest in the lower-social classes and the prevalence of risk factors in colon cancer was highest in the higher-social classes). The risk of leukemia was increased among patients with cancers of the breast, endometrium, and thyroid (possibly due to irradiation). There was a high relative risk of salivary gland cancer among patients with skin cancer other than melanoma or basal cell carcinoma in both sexes. The relative risk of a new primary cancer decreased with increasing age at diagnosis of the first cancer. The length of follow-up was positively associated with the relative risk of many cancers, although this finding was not as consistent as that with age.
TL;DR: The results indicate that primary radiation therapy provides a high likelihood of local tumor control and the analysis of failure suggests methods for decreasing each type of local recurrence.
Abstract: Primary radiation therapy has become an accepted alternative to mastectomy for patients with early breast cancer. In order to improve the results of this treatment, we performed an analysis of failure on 366 clinical Stage I or II invasive breast carcinomas treated with primary radiation therapy. With a median follow-up of 52 months, there have been 30 recurrences in the treated breast, for a 5 year actuarial local recurrence rate of 9%. The recurrence rate was much higher for patients having less-than-excisional biopsy than for those undergoing excisional biopsy (35% vs. 7%, p < 0.0001). Failures in the treated breast have been categorized as: true recurrence (TR), directly at the site of the primary; marginal miss (MM), at the edge of the boosted volume; and elsewhere in the breast (E). For patients having excisional biopsy, the actuarial probability of a true recurrence at 5 years was 4%. The risk of a true recurrence was related to the dose given to the primary site with rare true recurrences seen with doses greater than 6000 rad. The probability of a marginal miss at 5 years was 4%, and was not related to the dose or volume of the boost used. The probability of a recurrence elsewhere in the breast at 5 years was 1%. In patients treated with excisional biopsy and a total primary dose over 6000 rad, the probability of a local recurrence at 5 years was 4 and 10% for clinical Stage I and II patients respectively. These results indicate that primary radiation therapy provides a high likelihood of local tumor control and our analysis of failure suggests methods for decreasing each type of local recurrence.
TL;DR: Oestrogen receptor concentrations were measured in primary tumours of 291 postmenopausal breast cancer patients with high risk of recurrence and showed that patients with an oestrogen-receptor content below 100 f Mol/mg did not benefit from the endocrine therapy, while those with concentrations above 100 fmol/mg had a significantly longer recurrence-free survival.
TL;DR: The results suggest that DF3 antigen levels may be useful in distinguishing breast cancer patients from those with esophageal, gastric, colorectal, pancreatic, and lung carcinomas, as well as following the clinical course of patients with metastatic breast cancer.
Abstract: The murine monoclonal antibody (MAb), designated DF3, reacts with a 300,000-mol wt mammary epithelial antigen. A sequential double-determinant radioimmunoassay (RIA) has been developed to monitor circulating DF3 antigen. Using this assay, we have demonstrated that 33 of 36 normal women had plasma RIA antigen levels less than 150 U/ml. In contrast, 33 of 43 patients (76%) with metastatic breast cancer had RIA DF3 antigen levels greater than or equal to 150 U/ml. The difference between these two groups was statistically significant (P less than 0.001). Similar results have been obtained with a double-determinant enzyme-linked immunoassay (EIA). Only 6 of 111 age-matched normal subjects had EIA DF3 antigens levels greater than or equal to 30 U/ml, while 42 of 58 patients (72%) with breast cancer had levels equal to or above this value. Thus, similar patterns of specificity are obtained with the EIA or RIA. The elevation of circulating DF3 antigen levels in breast cancer patients has been confirmed by transfer blot assays. MAb DF3 reactivity occurred predominantly with circulating antigens of three different molecular weights ranging from 300,000 to approximately 400,000 mol wt. We also demonstrate that patients with both primary and metastatic breast cancer who were free of detectable disease at the time of sampling have DF3 antigen levels that are similar to those obtained from normal subjects. While patients with hepatoma (27%) and ovarian carcinoma (47%) also had elevated circulating DF3 antigen levels, the results suggest that DF3 antigen levels may be useful in distinguishing breast cancer patients from those with esophageal, gastric, colorectal, pancreatic, and lung carcinomas. Furthermore, the results of the RIA, EIA, and transblot analyses demonstrate that the measurement of circulating DF3 antigen levels provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer.
TL;DR: A biologic relationship between systemic sclerosis and certain malignant neoplasms is suggested, which occurred in the setting of long-standing pulmonary fibrosis but was not associated with cigarette smoking.
Abstract: The association between systemic sclerosis and malignancy was evaluated in the Pittsburgh standard metropolitan statistical area during 1971-1982 and compared with data for this geographic area from the Third National Cancer Survey of 1969-1971. Fourteen malignancies were detected in 262 systemic sclerosis patients (5%) during a followup period that included 1,335 patient-years. After adjustment for age and sex, the expected number of malignancies was 7.72 (relative difference = 1.81; P = 0.05). This increased relative difference was predominantly due to an increase in observed lung cancer (relative difference = 4.4; P less than 0.05), which occurred in the setting of long-standing pulmonary fibrosis but was not associated with cigarette smoking. Although breast cancer was no more frequent than expected, it tended to occur in close temporal relationship with the onset of systemic sclerosis. These findings suggest a biologic relationship between systemic sclerosis and certain malignant neoplasms.
TL;DR: The findings indicate that hematologic disorders are side effects of both radiation and alkylating agents used in the adjuvant treatment of primary breast cancer and the benefit from adjUvant chemotherapy for breast cancer exceeds the risk of leukemia.
Abstract: Since 1971, 8,483 women with primary breast cancer participated in seven trials evaluating adjuvant chemotherapy. Leukemia occurred in only three of 2,068 patients treated by operation alone. The cumulative risk was 0.06% after 10 years in those free of metastases or a second primary tumor, and 0.27% in those with tumor. Thus, leukemia is not an important factor in the natural history of breast cancer. Five of 646 women receiving postoperative regional radiation developed leukemia, an overall risk of 1.39 +/- .49% at 10 years. Twenty-seven cases of leukemia (0.5%) and seven of myeloproliferative syndrome (0.1%) were recorded in 5,299 patients who received L-phenylalanine mustard (L-PAM)-containing regimens. The maximum cumulative risk of leukemia in chemotherapy recipients (leukemia of any type and myeloproliferative syndrome) was 1.68 +/- .33% at 10 years following operation. The risk excluding those with myeloproliferative syndrome was 1.29 +/- .28%. The risk of leukemia in patients free of metastases or a second primary was 1.11 +/- .30% at 10 years, and when combined with myeloproliferative syndrome, it was 1.54 +/- .36%; risks not significantly greater than observed following radiation (P = .58 and .29). No cases of leukemia were observed during the 2 years of chemotherapy and none have occurred after the seventh postoperative year. Comparisons with the surveillance, epidemiology, and end results tumor registries (SEER) data indicate an increased relative risk of acute myelogenous leukemia following postoperative regional radiation (P less than .01) and adjuvant chemotherapy (P less than .001). The findings indicate that hematologic disorders are side effects of both radiation and alkylating agents used in the adjuvant treatment of primary breast cancer. The risk of such events is lower than that reported following treatment of other solid tumors and hematologic malignancies by chemotherapy. The benefit from adjuvant chemotherapy for breast cancer exceeds the risk of leukemia. Since chemotherapy is not uniformly beneficial, efforts should be directed toward identifying responders so that only those who will benefit are exposed to the risk.
Journal Article•
TL;DR: The relevance of cell kinetics of the primary tumor as a marker of biologic aggressivity was verified on a series of 258 patients with operable breast cancer without nodal and distant metastases who underwent radical mastectomy, showing the relevance of the kinetic variable as an important prognostic marker in breast cancer.
Abstract: The relevance of cell kinetics of the primary tumor as a marker of biologic aggressivity was verified on a series of 258 patients with operable breast cancer without nodal and distant metastases, who underwent radical mastectomy without any other treatment until relapse. The cell proliferative rate, evaluated in vitro on fresh tumor material and expressed as 3H-thymidine labeling index, was found to be an important discriminant of metastatic potential. Patients with slowly proliferating tumors showed a higher probability of 6-year relapse-free survival in comparison to those with fast-proliferating tumors (80.5% versus 59.6%, P = 0.00004). This finding was true for premenopausal and paramenopausal (P = 0.00005) as well as for postmenopausal patients (P = 0.01). The kinetic variable was also a discriminant of 6-year survival for the overall series (P = 0.003) and for premenopausal and paramenopausal patients (P = 0.003) regardless of the type of treatment after relapse. These findings show the relevance of the kinetic variable as an important prognostic marker in breast cancer.