Takuma Nemoto

Management and survival of female breast cancer: Results of a national survey by the American college of surgeons

This is a resume of a Breast Cancer Survey carried out by the American College of Surgeons in 1978. Four hundred and ninety‐eight hospitals in 47 states, Washington, D. C., and Puerto Rico participated, contributing a total of 24,136 female patients with histologically confirmed breast cancer. In these patients, five‐year cure rates were 60.5% for clinically localized disease and 33.9% for regional disease. Five‐year survival rates were 72.8% for localized disease and 49.1% for regional disease. From the 1960s into the early 1970s, there was a gradual shift away from radical mastectomy towards so‐called modified radical mastectomy. In a group of patients treated by either radical or modified mastectomies, the axillary nodal status, size of the tumor, and location of the tumor were examined in relation to the prognosis. In the study of number of metastatic nodes in the axilla, there were reduced cure and survival rates in patients with one or more positive nodes as compared to those with negative axillary nodes. With the increase in the number of positive nodes, there was a continuing associated decline in survival and cure. The clinical size of the tumor also correlated well to the prognosis. With the increase in the size of the tumor, there was a gradual increase in the probability of axillary nodal involvement. However, in the group of patients with tumor size smaller than 1 cm, axillary metastasis occurred in 25%. When the axillary nodes were involved, the cure rate in those patients was not significantly better than the rates for those with larger primary tumors in this study. Tumors located in the medial half of the breast were associated with a slightly lower cure rate than those in the lateral half. Young women under 35 years of age had poorer survival and cure rates, although in women 35–44 years of age, the five‐year results were comparable to the older group of patients. In blacks, breast cancer was diagnosed in a relatively more advanced stage than in whites. Survival and cure rates were generally lower for blacks, and such lower rates seem to be associated with the relatively advanced stage of the disease.

Chemotherapy induces regression of brain metastases in breast carcinoma

This study improves treatment options and ultimately survival by using systemic chemotherapy in brain metastases from breast carcinoma, since most of these patients have disseminated disease and a dismal prognosis when treated by conventional brain irradiation alone. One hundred consecutive patients with symptomatic brain metastases documented by radionuclide and/or computerized tomography scan were treated with systemic chemotherapy. Fifty of 100 patients demonstrated an objective response of brain metastases which was similar for extracranial metastases. There were 10 complete responders (CR), 40 partial responders (PR), 9 stable, and 41 nonresponders. Median duration of remission was 10+ months for CR and 7 months for PR (range, 2–72 months). Primary chemotherapy of brain metastases yielded responses in 27 pf 52 patients (52%) treated with Cytoxan (cyclophosphamide) (C), 5‐fluorouracil (F) and prednisone (P); 19 of 35 (54%) receiving CFP‐methotrexate (M) and vincristine (V); 3 of 7 (43%) treated with MVP, and 1 of 6 (17%) receiving Cytoxan plus Adriamycin (doxorubicin) (CA). Thirteen of 35 patients (37%) who subsequently had relapse of brain metastases were retreated successfully with secondary chemotherapy. The median survival for CR and PR was 39.5 months and 10.5 months, respectively, in contrast with nonresponder patients who had a median survival of 1.5 months. Thirty‐one percent of all treated patients survived more than 12 months. These findings suggest that the chemotherapeutic agents used penetrate the blood‐brain barrier inducing regression of brain metastases. This approach offers a significant benefit by simultaneously controlling extracranial disease, improving the response and prolonging survival.

Race‐related differences in breast cancer patients results of the 1982 national survey of breast cancer by the american college of surgeons

Data from the 1982 breast cancer survey of the American College of Surgeons were used to evaluate factors related to clinical, epidemiologic, and survival differences between black and white patients. Breast cancer in blacks was not discovered as early as in whites. Distribution of pathologic types of tumors were similar for both races with the exception of medullary carcinoma, which was more frequent in blacks than in whites. Estrogen receptor‐positive tumors were found significantly less frequently in blacks compared with whites. Survival was better for whites compared with blacks within each axillary nodes group 0, 1 to 3, and 4+. Black women with negative or positive estrogen receptors had lower survival rates than white women of the same receptor status. A regression analysis using Coxs proportional hazards model showed race, clinical stage or axillary nodal status, age at diagnosis, and estrogen receptor status as significant predictors of survival. Significant differences between black and white patients were also observed with respect to the report of family history of breast cancer, age at first pregnancy, number of pregnancies, and age at cessation of menses. Cancer 56: 1704‐1709, 1985.

Breast cancer risk, meat consumption and N‐acetyltransferase (NAT2) genetic polymorphisms

Although inconsistencies exist, some studies have shown that meat consumption is associated with breast cancer risk. Several heterocyclic amines (HAs), formed in the cooking of meats, are mammary carcinogens in laboratory models. HAs are activated by polymorphic N‐acetyltransferase (NAT2) and rapid NAT2 activity may increase risk associated with HAs. We investigated whether ingestion of meat, chicken and fish, as well as particular concentrated sources of HAs, was associated with breast cancer risk, and if NAT2 genotype modified risk. Caucasian women with incident breast cancer (n = 740) and community controls (n = 810) were interviewed and administered a food frequency questionnaire. A subset of these women (n = 793) provided a blood sample. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine NAT2 genotype. Consumption of red meats, as well as an index of concentrated sources of HAs, was not associated with increased breast cancer risk, nor did risk vary by NAT2 genotype. In post‐menopausal women, higher fish consumption was inversely associated with risk (odds ratio = 0.7; 95% confidence interval, 0.4–1.0); among pre‐menopausal women, there was the suggestion of inverse associations between risk and pork and chicken intake. Our results suggest that consumption of meats and other concentrated sources of HAs is not associated with increased breast cancer risk. However, due to the strong biologic plausibility for a role of some HAs in mammary carcinogenesis, and the likely measurement error in evaluation of sources of HAs in this study, further studies of these possible relationships are warranted. Int. J. Cancer75:825–830, 1998. Published 1998 Wiley‐Liss, Inc.

Factors affecting recurrence in lumpectomy without irradiation for breast cancer

Between 1980 and 1988, 122 women with operable invasive breast cancers underwent wide excision and axillary dissection without subsequent irradiation. During the follow‐up period of 1 to 8 years (median, 4 years), recurrences were observed in 23 patients (19%), 22 occurring in the breast and one in the axilla. This is a significant rate of recurrence and supports the need for breast irradiation after conservative surgery. The incidence of recurrence in the breast did not appear to be related to the presence or absence of axillary nodal metastasis. No recurrences were noted in 20 patients whose primary tumors were smaller than 1 cm. The incidence of recurrence was directly correlated to the increasing size of the tumor, but it also appeared to decrease with advancing age. In 31 patients over 70 years of age, only one (3%) recurrence was observed. If these early findings are confirmed, it is likely that patients with tumors smaller than 1 cm or patients over 70 years of age may be spared breast irradiation after wide excision.

Lifetime alcohol consumption and risk of breast cancer

The relation of lifetime alcohol intake to risk of breast cancer in pre- and postmenopausal women was examined in a case-control study in western New York. Cases with incident primary histologically confirmed breast cancer diagnosed during the period 1986-1991 (n = 740) and controls, frequency age-matched women drawn from New York state drivers license records (age < 65 yrs) and from records of the Health Care Finance Administration (age > or = 65 yrs, n = 810), were interviewed regarding intake of wine, beer, and hard liquor 2, 10, and 20 years ago and at 16 years of age. Although women in this study had generally low intakes of alcohol, there was little evidence of increased risk of breast cancer with intake of alcohol at any of the time periods or with an index of total lifetime intake. There was a weak indication of an increase in risk with beer for intakes of at least one drink per day. This risk was evident for 2, 10, and 20 years ago but not at 16 years of age. In this group with relatively low intakes of alcohol, evidence was weak for an association of increased risk of breast cancer with intake of alcohol, with the possible exception of a weak association with beer intake.

Exposure to breastmilk in infancy and the risk of breast cancer.

Early childhood nutrition may affect the subsequent risk of breast cancer in adulthood. We examined the association of having been breastfed with risk of breast cancer in a case-control study of women age 40–85 years in western New York. Cases (N = 528) had newly diagnosed primary, pathologically confirmed breast cancer; controls (N = 602) were randomly selected from the same community and were frequency matched on age. Having been breastfed was associated with decreased risk. The multivariate adjusted odds ratio was 0.74, and the 95% confidence interval was 0.56–0.99. We found little difference in the association for pre- and post-menopausal women despite a much higher frequency of breastfeeding among the older women. These findings indicate that early nutriture in general and bottle feeding in particular may relate to breast cancer development in adult-hood.

Breast cancer in the medial half. Results of 1978 National Survey of the American College of Surgeons.

In their previous report on the 1978 survey of breast cancer by the American College of Surgeons, the authors observed that the five‐year cure rate was lower, but only marginally, in patients having tumors located in the medial half of the breast than those in the lateral half. In order to identify factors which might explain this difference, as well as to evaluate the contribution of additional irradiation towards improving the cure rates, further analysis was made of the group of 9401 women in the long‐term survey, with particular attention to the size of the tumor, the age of the patient, and the extent of the nodal metastasis. This analysis demonstrates that the prognosis is quite similar between groups of patients with tumors in medial or lateral half of the breast. Irradiation given in addition to mastectomy did not appear to improve the prognosis of the patients as compared to that of those treated by mastectomy alone.

A cytochrome P4502E1 genetic polymorphism and tobacco smoking in breast cancer

Known breast‐cancer risk factors account for only part of the variability in breast‐cancer incidence. Tobacco smoke is not commonly considered a breast carcinogen, but many of its constituents, such as N‐nitrosamines, are carcinogenic in laboratory animal studies. Herein, we assessed a cytochrome P4502E1 (CYP2E1) genetic polymorphism (a Dral restriction enzyme site in intron 6) as a risk factor for breast cancer in both premenopausal and postmenopausal women. Because N‐nitrosamines are metabolically activated by CYP2E1, the risk among women smokers was investigated. Caucasian women were enrolled in a case‐control study of breast cancer between 1986 and 1991. A subset of the women (219 premenopausal and 387 postmenopausal women) consented to phlebotomy. The allelic frequencies for the premenopausal women (D allele = 0.91 and C allele = 0.09) and postmenopausal women (D allele = 0.93 and C allele = 0.07) were similar to those previously reported. There was no statistically significant association between the CYP2E1 polymorphism and breast‐cancer risk for premenopausal or postmenopausal women (adjusted odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.48, 2.24, and OR = 1.01, 95% CI = 0.55, 1.84, respectively). When the women were categorized as nonsmokers versus smokers (those who smoked more than one cigarette per week for more than 1 yr), premenopausal women with one or two C alleles who had a history of smoking were found to be at increased risk (unadjusted OR = 7.00, 95% CI = 0.75, 14.53, and adjusted OR = 11.09, 95% CI = 1.51, 81.41), although the number of study subjects with those genotypes was small. The small number of study subjects with a C allele precluded meaningful classification by level of smoking, but categorizing the smokers into two groups (above and below the median) also suggested an increased risk. Premenopausal women with the DD genotype and postmenopausal women with any genotype were not at increased risk. Breast‐cancer risk was not related to the CYP2E1 genotype in either premenopausal nonsmokers or smokers (adjusted OR = 0.66, 95% CI = 0.20, 2.17, and OR = 2.13, 95% CI = 0.60, 7.59, respectively) or postmenopausal nonsmokers or smokers (OR = 0.90, 95% CI = 0.34, 2.35, and OR = 1.02, 95% CI = 0.46, 2.23, respectively), although the difference in the ORs for premenopausal nonsmokers and smokers suggests an increased risk for smokers. While there are limitations to this study, particularly related to the small number of subjects with the DC and CC genotypes, the study suggests that some women may be susceptible to tobacco smoke because of a CYP2E1 polymorphism. However, these results are preliminary and must be replicated.

Management of brain metastases from breast cancer by combination chemotherapy

SummarySince most patients with brain metastases from breast cancer have disseminated disease elsewhere and a dismal prognosis when treated by whole brain irradiation alone, we investigated the use of systemic chemotherapy in 66 such patients. Fifty-two percent (34 of 66 patients) demonstrated an objective response to this therapy which was similar to the results obtained in patients treated for extracranial metastases. Eighteen patients who subsequently had recurrence of brain metastases were successfully retreated with secondary chemotherapy. The median duration of remission in 34 responders was ten months. The median survival, from the time of chemotherapy for brain metastases, was 13.1 months in 34 responders (range 5–74+) vs. 3.0 months in 32 non-responders (P < 0.001).These findings suggest that systemic chemotherapy is effective in the treatment of patients with brain metastases from breast cancer by inducing remission and prolonging survival.