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Objective: The suggestion that breast cancer management is compromised in elderly patients had prompted our review of the results of policies regarding screening and early detection of breast cancer and the adequacy of primary treatment in older women (> or = 65 years of age) compared to younger women (40 to 64 years of age)., Summary Background Data: Although breast cancer in elderly patients is considered biologically less aggressive than similar staged cancer in younger counterparts, outcome still is a matter of stage and adequate treatment of primary cancer. For many reasons, physicians appear reluctant to treat elderly patients according to the same standards used for younger patients. There is even government-mandated alterations in early detection programs. Thus, since 1993, Medicare has mandated screening mammography on a biennial basis for women older than 65 year of age compared to the current accepted standard of yearly mammograms for women older than 50 years of age. Using State Health Department and tumor registry data, the authors reviewed screening practice and management of elderly patients with primary breast cancer to determine the effects of age on screening, detection policies (as reflected in stage at diagnosis), treatment strategies, and outcome., Methods: Data were analyzed from 5962 patients with breast cancer recorded in the state-wide Tumor Registry of the Hospital Association of Rhoda Island between 1987 and 1995. The focus of the data collection was nine institutions with established tumor registries using AJCC classified tumor data. Additional data were provided by the State Health Department on screening mammography practice in 2536 women during the years 1987, 1989, and 1995., Results: The frequency of mammographic screening for all averaged 40% in 1987, 52% in 1987, and 63% in 1995. In the 65-year-old and older patients, the frequency of screening was 34% in 1987, 45% in 1989, and 48% in 1995, whereas in the 40- to 49-year-old age group, the frequency of mammography was 47% in 1987, 61% in 1989, and 74% in 1995 (p < 0.001). There was a lower detection rate of preinvasive cancer in the 65-year-old and older patients, 8.8% versus 13.7% in patients within the 40- to 64-year-old age group (p < 0.001). There was a higher percentage of treatment by limited surgery among elderly patients with highly curable Stage IA and IB cancer with 26.6% having lumpectomy alone versus 9.4% in the younger patients. Five-year survival in that group was significantly worse (63%) than in patients treated by mastectomy (80%) or lumpectomy with axillary dissection and radiation (95%, < 0.001). A similar effect was seen in patients with Stage II cancer., Conclusions: Breast cancer management appears compromised in elderly patients (older than 65 years of age). Frequency of mammography screening is significantly less in elderly women older than 65 years of age. Early detection of preinvasive (curative cancers) is significantly less than in younger patients. The recent requirement by Medicare of mammography every other year may further reduce the opportunity to detect potentially curable cancers. Approximately 20% of patients had inferior treatment of favorable stage early primary cancer with worsened survival. Detection and treatment strategy changes are needed to remedy these deficiencies.

Background: Axillary dissection has maintained a role of primacy for the surgical therapy of invasive carcinoma of the breast for many years. More recently, early (T1) minimally invasive carcinoma of the breast has been diagnosed with increasing frequency, and the necessity of axillary dissection for sampling purposes in these small tumors has been questioned, based primarily on the finding of low rates of axillary metastases., Study Design: The Rhode Island State Tumor Registry records of 1,126 patients with T1a or T1b tumors were examined to assess the effect of axillary dissection on patient outcome. These data span 9 years (1985 to 1992) with a median follow-up duration of 64 months. Five-year overall, disease-free, and breast cancer-specific (determinate) survival were determined according to treatment modality. Axillary node positivity was calculated for patients with minimally invasive carcinoma of the breast who underwent axillary dissection. Multivariate statistical methods were used to provide adjustment for known confounding prognostic variables., Results: Omission of axillary dissection occurred in 157 cases and correlated with reductions in overall, disease-free, and breast cancer-specific survival (p < .001 in all cases). Nodal status significantly influenced disease-free survival in minimally invasive carcinoma of the breast (90 percent node-negative compared with 76 percent node-positive, p = .02). Nodal positivity was evident in 18.2 percent of patients undergoing axillary dissection for minimally invasive carcinoma of the breast (9.8 percent for T1a, 19.4 percent for T1b, p = .01). In multivariate analysis, the performance of axillary dissection with breast conservation or modified radical mastectomy were independent predictors of overall survival, as well as disease-free and breast cancer-specific survival., Conclusions: A significant number of patients with small (less than or equal to 1 cm) invasive tumors of the breast will have axillary metastases at the time of diagnosis. Omission of axillary dissection in these patients was associated with significant impairment of overall, disease-free, and breast cancer-specific survival. Axillary dissection should continue to be a standard approach for the surgical therapy of all patients with invasive carcinoma of the breast, regardless of tumor size.

Objective: A refinement of prognostic variables using traditional pathologic markers integrated with oncogene proteins, enzymes, and hormonal factors may enhance the ability to predict for recurrence or survival in patients with mammary carcinoma. Although various oncogenes and oncogene products have been identified in human breast carcinoma, their relationship to disease outcome remains controversial., Methods: Using the monoclonal antibodies cS93.1, 9E1.0, F235-1.7.1, and PAb 1801 against each oncogene protein studied, the avidin-biotin complex immunoperoxidase method provided immunohistochemical staining of bound oncogene protein for c-fos, c-myc, Ha-ras, and p53, respectively. Analyses were made on archival pathology tissues of 85 breast cancer patients (stages I, IIA, and IIB). Forty patients (47%) had recurrence of disease; 45 remained free of local-regional or distant disease at mean follow-up of 48 months (range 6-180 months). Molecular biological data were merged with clinicopathologic demographics 1) to determine the frequency of single or co-expression of oncogenes in this patient population; 2) to evaluate the value of these molecular protein markers to predict probability of recurrence; and 3) to determine worth of the studied oncogenes to correlate with traditional clinical pathologic parameters and overall survival., Results: In this study, oncogene expression had statistical correlation for recurrence with increasing co-expression: one oncogene 17.2%, two oncogenes 56.3%, three or four oncogenes, 100% (p = 0.001). Increasing oncogene or co-oncogene expression correlated with statistically significant reduction in disease-free and overall survival; with no expression of oncogenes, disease-free survival was 30 (SE +/- 5.7) months and overall survival was 56.4 (SE +/- 4.57) months. With expression of three oncogenes, disease-free survival was 12 (SE +/- 1.23) months (p = 0.0018) and overall survival was 23.4 (SE +/- 3.38) months (p = 0.0025). In univariate Wilcoxon analysis, oncogene expression was the most significant variable to determine survival (p = 0.035); in multivariate analysis, age and oncogene co-expression each emerged as the most significant variables for overall survival. For the proportional hazards regression model, oncogene co-expression was significant (p = 0.0104, risk-ratio 1.914) and correlated with age and tumor size as significant variables. Ha-ras and c-fos both emerged as important individual oncogene proteins to affect survival (p = 0.0925, risk-ratio 3.517 and p = 0.025, risk-ratio 4.214, respectively). The proto-oncogene c-myc and the antitumor suppressor gene p53 did not have significant effects as individual oncogenes to influence survival., Conclusions: Approximately one fifth of the breast cancer patients in this analysis (disease-free and recurrent) expressed only a single oncogene marker (c-fos, c-myc, Ha-ras, or p53); one quarter of patients with recurrent disease expressed only one oncogene protein. Single oncogene expression did not possess independent prognostic significance for prediction of recurrence. Further, p53 mutations did not function as independent correlates for prognosis. The co-expression of the studied proto-oncogenes (c-myc, Ha-ras) and the nuclear transcriptional protein (c-fos) functioned as a strong prognostic correlate for recurrence and survival; the effect of individual oncogenes to predict survival was greatest for Ha-ras and c-fos. Immediate or early co-expression of three oncogene proteins in neoplastic transformation endowed cells of invasive carcinoma with an aggressive phenotype. This aggressive phenotype was evident in a small percentage of the studied population (11%) and predicted adverse disease-free and overall survival. These findings suggest that oncogene co-expression possesses significant prognostic and potential therapeutic value; incorporation of this molecular technology into future prospective randomized trials is advisable.

Ductal carcinoma in situ (DCIS) is an early, localized stage of breast carcinoma that has an excellent prognosis when it is properly treated. The significant increase in the frequency of diagnosis of DCIS in recent years is the result of both better recognition of DCIS among pathologists and widespread use of screening mammography. Multicentricity, bilaterality and histologic subtype are important considerations in the management of this disease. The clinical presentation of DCIS is the presence of either a palpable mass or a mammographic abnormality, most frequently in the form of an area of microcalcifications. For several decades, total mastectomy was considered the appropriate treatment for DCIS, and it should still be considered the standard to which more conservative forms of treatment must be compared. Breast conservation surgery has been used with increasing frequency in the treatment of DCIS but the adequacy of this approach remains subject to controversy. Segmental mastectomy alone may be applied with caution in carefully selected patients, while the rest of the patients undergoing breast conservation surgery should be treated with breast irradiation. Axillary node dissection is generally considered unnecessary in the treatment of DCIS. There is no role for adjuvant chemotherapy in the management of this disease. The role of tamoxifen in the treatment of DCIS is not clearly defined and it should be given only to patients enrolled in clinical trials. Ongoing research should clarify the controversies surrounding DCIS and enable us to define the optimal management for this disease.

A retrospective review of 483 women who had metastatic breast cancer and were treated between 1942 and 1975 was carried out to examine the effects of improving and aggressive palliative modalities on patient survival. There was a steady increase in the proportion of patients treated by chemotherapy and/or hormonal ablative therapy. Additive hormonal therapy, irradiation, and surgery for palliation decreased in frequency during the same period. Survival time from the first recurrence did not appear to increase in these patients over the period of this study. In spite of increasingly sophisticated palliative therapies, the survival time of patients with metastasis did not appear to be significantly prolonged.