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N Wolmark

Publications and source records attributed to N Wolmark.

At least 91 records · Page 5Linked to original sources
PubMed1987

Endogenous sex hormone levels and breast cancer risk.

Sex-steroid hormones are a major determinant of the risk of breast cancer. We evaluated the relationship between obesity and endogenous estrogen levels in 79 healthy, postmenopausal women. Thirty-nine of the women were siblings of patients with postmenopausal-onset breast cancer; the remaining women were age-matched (+/- 10 yr) controls. Our hypothesis was that the siblings of the breast cancer patients would weigh more and that this excess weight would lead to higher serum estrone levels. The choice of unaffected family members of breast cancer patients reduces the concern that results may have been influenced by the cancer rather than antecedent to its development. Our findings demonstrated a statistically significant excess estrone level in the siblings compared to the controls (58.9 vs 47.8 pg/ml, P = 0.005). The siblings weighed 4.3 kg more than the controls. Matched pairs analysis (sibling-control), adjusting for weight, also showed significant differences in serum estrone levels. These differences were observed despite comparability in dietary intake, medication use, and personal medical history. These findings represent the first time that higher estrogen levels have been measured in siblings of postmenopausal breast cancer patients. This observation may represent an important link in our understanding of the relationship between genetic and environmental risk factors of breast cancer. One approach to subsequent genetic studies of breast cancer may be to focus on the possible biological determinants such as sex-steroid hormone level receptors, oncogenes, and gene products and not on the "familial aggregation" of breast cancer.

Aged↗
PubMed1987

Prolonging tamoxifen therapy for primary breast cancer. Findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial.

OBJECTIVE: To determine whether prolonging the duration of tamoxifen administration beyond the cessation of a combined chemotherapy regimen benefits patients with primary breast cancer with positive findings in axillary nodes who benefit initially from the combined regimen. DESIGN: Nonrandomized, nonconcurrent cohort study. SETTING: National Surgical Adjuvant Breast and Bowel Project, conducted in 68 institutions in North America. PATIENTS: Women were included if they had breast cancer with positive nodes and were aged 49 years or less with both estrogen and progesterone receptor levels of 10 fmol or more, aged 50 to 59 years with progesterone receptor levels of 10 fmol or more, or aged 60 to 69 years. Two cohorts were compared: patients who were randomly assigned to the tamoxifen arm of the adjuvant chemotherapy trial (randomized patients) and women who were added to this arm after randomization had ceased (registered patients). Three hundred seventy-seven women in each group who were disease free at the end of the initial 2-year treatment period were followed for an additional 3 years. INTERVENTIONS: All received melphalan, fluorouracil, and tamoxifen (10 mg twice daily by mouth) for 2 years. Registered patients (but not randomized patients) were offered tamoxifen for a third year after the initial 2-year treatment period, and 273 (72%) agreed. MEASUREMENTS AND MAIN RESULTS: Women receiving a third year of tamoxifen had a better disease-free survival rate (odds ratio, 1.54; 95% confidence interval, 1.14 to 2.07; p = 0.004) and survival rate (odds ratio, 1.56; 95% Cl, 1.02 to 2.37; p = 0.04) through their fifth postoperative year. Women aged 50 years or more benefited, but those aged 49 years or less did not. CONCLUSIONS: The benefit of tamoxifen given to tamoxifen-responsive patients in conjunction with melphalan and fluorouracil appears to be enhanced when the tamoxifen treatment is continued beyond cessation of treatment with these agents.

Actuarial Analysis↗
PubMed1986

A comparison of stapled and handsewn anastomoses in patients undergoing resection for Dukes' B and C colorectal cancer. An analysis of disease-free survival and survival from the NSABP prospective clinical trials.

This study was to assess the effect of stapled colorectal anastomoses on local recurrence, disease-free survival, and survival following curative resection for Dukes' B and C adenocarcinoma. Data were derived from two randomized prospective trials of the National Surgical Adjuvant Breast and Bowel Project designed to evaluate the efficacy of adjuvant therapy in colorectal cancer. Of 1111 patients with colonic anastomoses, 255 were stapled mechanically. There were no significant differences in disease-free survival, survival, or local tumor recurrence among patients subjected to stapled or handsewn anastomoses. Of the 181 patients undergoing anterior resection for rectal cancer, 82 anastomoses were fashioned with staples. No significant disadvantage in disease-free survival, survival, or local recurrence could be attributed to use of the mechanical stapling devices. Twelve percent of patients undergoing stapled rectal anastomoses developed a local recurrence as a first sign of treatment failure compared with 19 percent for the handsewn group. No significant differences in the length of distal margins were detectable. The average time on study was 41 months. The use of stapled anastomoses for carcinoma of the colon or rectum is not associated with an adverse effect on long-term outcome.

Adenocarcinoma↗
PubMed1986

The prognostic value of the modifications of the Dukes' C class of colorectal cancer. An analysis of the NSABP clinical trials.

This study was carried out in an effort to resolve the dilemma created by three proposed modifications of the Dukes' C class of colorectal cancer. Each modification is based on a separate prognostic discriminant characterized by: the level of histologically positive nodes, the depth of tumor penetration, and the number of histologically positive nodes. Data were derived from 844 patients with Dukes' C lesions randomized into two prospective clinical trials of the NSABP; the mean time on study was 41 months. Analysis of the three modifications as independent variables without regard for possible confounding effects disclosed that each had a highly significant predictive capacity. When each discriminant was examined, this time adjusting for the contribution of the other two discriminants, the effect attributable to the level of positive nodes was markedly attenuated. Thus, the level of positive nodes provided little information over and above that of depth of tumor penetration and the number of positive nodes. Of the two latter discriminants, although both were significant predictors of survival, the number of positive nodes appeared to be the strongest factor. Using both depth of penetration and the number of positive nodes, a unique Dukes' C subset of patients could be identified with a prognosis at least as good as Dukes' B lesions; this group was characterized by partial tumor penetration and the presence of 1-4 positive nodes. It is concluded that both depth of penetration and the number of positive nodes represent appropriate modifications of the initial Dukes scheme, and one discriminant should not be used to the exclusion of the other. The data raise serious doubts relative to the propriety of newly proposed TNM classification schemes that fail to utilize the number of positive nodes as a predictive discriminant.

Carcinoma↗
PubMed1986

An analysis of survival and treatment failure following abdominoperineal and sphincter-saving resection in Dukes' B and C rectal carcinoma. A report of the NSABP clinical trials. National Surgical Adjuvant Breast and Bowel Project.

Abdominoperineal resections for rectal carcinoma are being performed with decreasing frequency in favor of sphincter-saving resections. It remains, however, to be unequivocally demonstrated that sphincter preservation has not resulted in compromised local disease control, disease-free survival, and survival. Accordingly, it is the specific aim of this endeavor to compare local recurrence, disease-free survival, and survival in patients with Dukes' B and C rectal cancer undergoing curative abdominoperineal resection or sphincter-saving resection. For the purpose of this study, 232 patients undergoing abdominoperineal resection and 181 subjected to sphincter-saving resections were available for analysis from an NSABP randomized prospective clinical trial designed to ascertain the efficacy of adjuvant therapy in rectal carcinoma (protocol R-01). The mean time on study was 48 months. Analyses were carried out comparing the two operations according to Dukes' class, the number of positive nodes, and tumor size. The only significant differences in disease-free survival and survival were observed for the cohort characterized by greater than 4 positive nodes and were in favor of patients treated with sphincter-saving resections. A patient undergoing sphincter-saving resection was 0.62 times as likely to sustain a treatment failure as a similar patient undergoing abdominoperineal resection (p = 0.07) and 0.49 times as likely to die (p = 0.02). The inability to demonstrate an attenuated disease-free survival and survival for patients treated with sphincter-saving resection was in spite of an increased incidence of local recurrence (anastomotic and pelvic) observed for the latter operation when compared to abdominoperineal resection (13% vs. 5%). A similar analysis evaluating the length of margins of resection in patients undergoing sphincter-preserving operations indicated that treatment failure and survival were not significantly different in patients whose distal resection margins were less than 2 cm, 2-2.9 cm, or greater than or equal to 3 cm. If any trend was observed, it appeared that patients with smaller resection margins had a slightly prolonged survival (p = 0.10). This observation was present in spite of the fact that local recurrence as a first site of treatment failure was greater in the group with less than 2 cm that it was in the greater than or equal to 3 cm category, 22% versus 12%. This increased local recurrence rate in the population with smaller margins was not translated into an in crease in overall treatment failure and had absolutely no influence on survival. It is suggested that local recurrence serves as a marker of distant disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Anal Canal↗
PubMed1986

Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial.

In this National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial, 1,891 women with primary operable breast cancer and positive axillary nodes were randomized between Jan, 1977 and May 1980 to receive L-phenylalanine mustard (L-PAM) and 5-fluorouracil (5-FU) either with or without tamoxifen (TAM)-PFT. This report presents life table probabilities, cumulative odds ratios, and P values for disease-free survival (DFS) and survival at yearly intervals through 5 years of observation (mean time on study, 72 months). When patients were examined overall without regard for any discriminant associated with outcome, ie, age, number of positive nodes, or tumor receptor status, there was a significant prolongation of DFS (P = .002), but not survival through the fifth postoperative year. The benefit was almost entirely restricted to those greater than or equal to 50 years with greater than or equal to 4 positive nodes. In that group there was a 66% greater chance of remaining disease free if PFT was received (P less than .001), and there was also a significant survival benefit (P = .02). The advantage from PFT was found to be associated with tumor estrogen receptor (ER) and progesterone receptor (PR) as well as patient age and nodal status. Overall there was a significant improvement in DFS from PFT in those having tumors with an ER or PR level greater than or equal to 10 femtomole (fmol) (P = .01 and .009, respectively). No significant benefit in DFS or survival has been observed in patients less than or equal to 49 years old related either to nodes or tumor receptor status. Survival continues to be adversely affected by TAM in those patients (less than or equal to 49 years old), particularly when their tumors have a PR of 0 to 9 fmol (P = .007). In patients greater than or equal to 50 years old with four or more positive nodes, a significant DFS benefit persisted through the fifth year of observation in those having tumor ER or PR levels greater than 10 fmol (P less than .001 and .002). The advantage was observed in patients 50 to 59 years old as well as those 60 to 70. Women in the older decade demonstrated some advantage from PFT when their tumor ER or PR was 0 to 9 fmol. The most likely explanation for this finding is analytical error in receptor analyses.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1986

Systemic adjuvant therapy in treatment of primary operable breast cancer: National Surgical Adjuvant Breast and Bowel Project experience.

This report provides an overview of information presented by us at a recent National Institutes of Health Consensus Development Conference on Adjuvant Chemotherapy. The data, derived from 7 randomized clinical trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) since 1958, permit us to conclude that the use of systemic adjuvant therapy is of benefit in both premenopausal and postmenopausal patients with primary breast cancer. Data from the first NSABP trial begun in 1958 with short-course perioperative thiotepa demonstrated a long-term survival benefit in premenopausal but not postmenopausal patients. Ten-year findings from a second trial evaluating response to melphalan (P) implemented in 1972 indicated that, when related to age and nodes, there was a benefit from this drug in both the 1-3 and greater than or equal to 4 positive node premenopausal groups but those with fewer nodes were most improved. In this group characterized by premenopausal women with 1-3 positive nodes, mortality was reduced 64% with a cumulative odds ratio of 3.25 (P = .009) at 10 years after surgery. When related to nuclear grade, there was a striking benefit in survival from P in patients less than or equal to 49 and greater than or equal to 50 years with undifferentiated tumors. The addition of 5-fluorouracil (F) to melphalan (PF) resulted in an increase in disease-free survival and survival over that observed with P in patients less than or equal to 49 and greater than or equal to 50 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer.

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.

Breast Neoplasms↗
PubMed1985

Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation.

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.

Breast Neoplasms↗
PubMed1985

Adjuvant therapy in primary breast cancer.

This article considers the role of adjuvant therapy in primary breast cancer, utilizing data from randomized prospective clinical trials as illustrative examples. The ongoing efforts targeted toward addressing some of the unresolved issues are underscored.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Minimal breast cancer: advance or anachronism?

The author argues that minimal breast cancer does not represent a distinct disease entity but comprises three discrete components, each with unique characteristics. The natural history of lobular carcinoma in situ and intraductal cancer, two of the components of minimal breast cancer, is described. The dangers of relying on a data base established on the strength of retrospective anecdotal information is underscored. Lobular carcinoma in situ has a propensity for multicentricity and bilaterality. In 25% of patients with lobular carcinoma in situ, invasive breast cancer will develop subsequently, and the majority of these tumours will be of ductal origin. The average interval from the diagnosis of lobular carcinoma in situ to the development of subsequent invasive cancer is over 15 years and both breasts are at equal risk. Based on this information, the use of bilateral prophylactic mastectomy is unjustified. In contrast to lobular carcinoma in situ, 25% to 50% of patients with intraductal carcinoma will subsequently have infiltrating cancer, at an average of 10 years after the initial biopsy. Although the putative incidence of multicentricity is 50%, virtually all subsequent invasive cancers occur not only in the same breast but in the same quadrant as the initial lesion. In light of the momentum for breast-preserving operations in invasive cancer, clinical trials should be implemented to assess the propriety of conservative management with and without radiotherapy in patients with intraductal carcinoma.

Adenocarcinoma↗
PubMed1985

Adjuvant chemotherapy in colorectal cancer.

The current status of adjuvant therapy for colorectal cancer is reviewed using examples from selected, recently completed, randomized, prospective, clinical trials. Although adjuvant systemic therapy is of limited therapeutic efficacy in cancer of the colon, there have been examples of beneficial effects in specific patient subsets. The rationale and current status of adjuvant portal vein hepatic perfusion suggest that it represents a potentially promising approach that must be evaluated in a large prospective randomized study. Finally, the value of adjuvant radiotherapy and chemotherapy for carcinoma of the rectum is assessed. Although one study has demonstrated increased disease-free survival for patients receiving a combination of chemotherapy and radiotherapy, the small numbers in the study preclude any definitive conclusions. The current National Surgical Adjuvant Breast Project, rectal protocol R-01, the largest rectal cancer study with a concomitant "untreated" control, is reviewed and discussed.

Combined Modality Therapy↗