Spread of human cancer cells occurs with probabilities indicative of a nongenetic mechanism.

There has been much uncertainty as to whether metastasis requires mutation at the time of spread. Here, we use clinical data to calculate the probability of the spread of melanoma and breast cancer cells. These calculations reveal that the probability of the spread of cancer cells is relatively high for small tumours (approximately 1 event of spread for every 500 cells for melanomas of 0.1 mm) and declines as tumours increase in size (approximately 1 event of spread for every 10(8) cells for melanomas of 12 mm). The probability of spread of breast cancer cells from the lymph nodes to the periphery is approximately 1 event of spread for every 10(8) cells in the nodal masses, which have a mean diameter of 5 mm, while the probability of spread of cancer cells from the breast to the periphery when the primary masses are 5 mm is also approximately 1 event of spread for every 10(8) cells. Thus, the occurrence of an event of spread from the breast to the lymph nodes appears not to increase the propensity of the progeny of those cells to spread from the lymph nodes to the periphery. These values indicate that the spread of human breast cancer and melanoma cells is unlikely to occur by a mechanism requiring mutation at the time of spread.

Palpable breast cancers are inherently different from nonpalpable breast cancers.

BACKGROUND: We examined the clinicopathologic profile of T1 cancers to determine whether palpable cancers are different from nonpalpable cancers. METHODS: A prospective database was reviewed. Palpable T1 cancers were compared with nonpalpable T1 cancers. Initial significance was determined by chi2 analysis. Factors found to be significant were then reanalyzed. controlling for tumor size by logistic or linear regression, as appropriate. RESULTS: Of 1263 T1 cancers treated between 1981 and 2000, 857 (68%) were palpable and 401 (32%) were nonpalpable. Palpability correlated with pathologic tumor size, mitotic grade, nuclear grade, high S-phase, lymphovascular invasion, nodal positivity, and lack of extensive intraductal component, multifocality, and multicentricity. There was no significant difference in estrogen receptor, progesterone receptor or Her-2/neu status, ploidy, or DNA index. Breast cancer-specific survival was worse for patients with palpable cancers. CONCLUSIONS: Palpable cancers are inherently different from nonpalpable cancers, with a less diffuse growth pattern, higher metastatic potential, higher proliferative activity, more nuclear abnormalities, and a worse prognosis.

The management of ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group of lesions with diverse malignant potential. It is the most rapidly growing subgroup within the breast cancer family with more than 42 000 new cases diagnosed in the United States during 2000. Most new cases are nonpalpable and are discovered mammographically. Treatment is controversial and ranges from excision only, to excision with radiation therapy, to mastectomy. Prospective randomized trials reveal an approximate 50% reduction in local recurrence rate overall with the addition of radiation therapy to excisional surgery, but the published prospective data do not allow the selection of subgroups in whom the benefit from radiation therapy is so small that its risks outweigh its benefits. Nonrandomized single facility series suggest that age, family history, nuclear grade, comedo-type necrosis, tumor size and margin width are all important factors in predicting local recurrence and that one or more of these factors could be used to select subgroups of patients who do not benefit sufficiently from radiation therapy to merit its use. When all patients with ductal carcinoma in situ are considered, the overall mortality from breast cancer is extremely low, only about 1-2%. When conservative treatment fails, approximately 50% of all local recurrences are invasive breast cancer. In spite of this, the mortality rate following invasive local recurrence is relatively low, about 12% with eight years of actuarial follow-up. Genetic changes routinely precede morphological evidence of malignant transformation. Lessons learned from ongoing basic science research will help us to identify those DCIS lesions that are unlikely to progress and to prevent progression in the rest.

Predicting axillary nodal positivity in 2282 patients with breast carcinoma.

Axillary lymph node status continues to be the single most important prognostic variable for breast cancer survival despite significant progress in the molecular and genetic characterization of breast malignancies. All patients with invasive breast cancer who underwent axillary lymph node dissection as part of their treatment were evaluated by 11 clinical and pathologic factors, including the primary lesion's T category (TNM staging system), whether the lesion was clinically palpable, the presence of lymphatic or vascular invasion, nuclear grade, estrogen and progesterone receptors, S-phase, age, HER2/neu overexpression, histology (infiltrating lobular or ductal), and ploidy. A total of 2282 axillary dissections were performed: 391 in patients with ductal carcinoma in situ (DCIS) [3 of which (0.8%) contained metastases] and 1891 in patients with invasive breast cancer [680 of which (36%) contained metastases]. Multivariate analysis of patients with invasive cancer identified four factors as independent predictors of axillary lymph node metastases: lymph/vascular invasion, tumor size, nuclear grade, tumor palpability. Among a group of 189 patients with nonpalpable, non-high-grade invasive lesions 15 mm or smaller without lymph/vascular invasion, only 6 (3%) had metastases to lymph nodes. If any three of the favorable factors were present, lymph node positivity was 6% or less. Clinical and pathologic feature of the primary lesions can be used to estimate the risk of axillary lymph node metastases. Such risk assessment can be used for the treatment decision-making process.

Breast cancer after augmentation mammoplasty.

BACKGROUND: It is thought that implants interfere with breast cancer diagnosis and that cancers in women who have had breast augmentation carry a worse prognosis. METHODS: A prospective breast cancer database was reviewed, comparing augmented and nonaugmented patients for details of histology, palpability, tumor size, nodal status, mammographic status, receptor status, nuclear grade, stage, and outcome. RESULTS: Ninety-nine cancers in augmented women and 2857 cancers in nonaugmented women were identified. Among these women, mammography was normal in 43% of those who had had augmentation and in 5% of those who had not. Augmented women were more likely to have palpable cancers (83% vs. 59%) and nodal involvement (48% vs. 36%), and less likely to have ductal carcinoma in situ (DCIS) (18% vs. 28%). When comparing only women younger than 50, the differences in invasiveness and nodal status lost significance. Cancers diagnosed in the 1990s were more likely to be nonpalpable and noninvasive than those diagnosed in the 1980s. This trend was more pronounced in the augmented population. CONCLUSIONS: Augmented patients were more likely to have palpable cancers, although the overall stage and outcome were similar to those of nonaugmented women. Although there have been significant improvements in our ability to diagnose early breast cancer over the past two decades, mammography continues to be suboptimal in augmented women.

Ductal carcinoma in situ of the breast.

Ductal carcinoma in situ of the breast is a heterogeneous group of lesions with diverse malignant potential. It is the most rapidly growing subgroup in the breast cancer family; it is projected that more than 39,000 new cases will be diagnosed in the United States during 1999. Most new cases are nonpalpable and are discovered mammographically. Treatment is controversial and ranges from excision only, to excision with radiation therapy, to mastectomy. Genetic changes routinely precede morphologic evidence of malignant transformation. Medicine must learn how to recognize these genetic changes, exploit them, and in the future, prevent them.

The Van Nuys Breast Center: the first free-standing multidisciplinary breast center.

This article describes the author's 30-year experience with the design and development of breast centers. It describes the author's initial attempt at developing a breast center at UCLA, the history of the Van Nuys Breast Center (its patient population, philosophy, problems, finances, and demise), and the development of the Harold E. and Henrietta C. Lee Breast Center. Breast centers are defined as focused multidisciplinary facilities of excellence, dealing with the complete range of breast problems. The main focus of this article is the Van Nuys Breast Center, which was the prototype model for most breast centers developed in the United States.

Not everyone with ductal carcinoma in situ of the breast treated with breast preservation needs post-excisional radiation therapy.

While the results of NSABP protocol B-17 and EORTC protocol 10853 prove that radiation therapy decreases the overall rate of local recurrence in patients with DCIS, there are clearly subgroups of patients who do not benefit from radiation therapy or whose benefit is so small that the addition of radiation therapy to their treatment regimen is simply not worthwhile. Identifying these subgroups is of paramount importance. Factors like tumour size, margin width, nuclear grade, and the presence or absence of comedonecrosis can be used to define favorable subgroups that do not require post-excisional radiation therapy. The most recent results of NSABP protocol B-17 and EORTC protocol 10853 confirm that, regardless of treatment, there is no difference in the single most important end-point: survival. If there is no difference in breast cancer mortality, it is clearly worthwhile to try to define the subgroups of patients who can be spared the time, costs, and side-effects of a treatment that they do not need.

The influence of margin width on local control of ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ is a non-invasive carcinoma that is unlikely to recur if completely excised. Margin width, the distance between the boundary of the lesion and the edge of the excised specimen, may be an important determinant of local recurrence. METHODS: Margin widths, determined by direct measurement or ocular micrometry, and standardized evaluation of the tumor for nuclear grade, comedonecrosis, and size were performed on 469 specimens of ductal carcinoma in situ from patients who had been treated with breast-conserving surgery with or without postoperative radiation therapy, according to the choice of the patient or her physician. We analyzed the results in relation to margin width and whether the patient received postoperative radiation therapy. RESULTS: The mean (+/-SE) estimated probability of recurrence at eight years was 0.04+/-0.02 among 133 patients whose excised lesions had margin widths of 10 mm or more in every direction. Among these patients there was no benefit from postoperative radiation therapy. There was also no statistically significant benefit from postoperative radiation therapy among patients with margin widths of 1 to <10 mm. In contrast, there was a statistically significant benefit from radiation among patients in whom margin widths were less than 1 mm. CONCLUSIONS: Postoperative radiation therapy did not lower the recurrence rate among patients with ductal carcinoma in situ that was excised with margins of 10 mm or more. Patients in whom the margin width is less than 1 mm can benefit from postoperative radiation therapy.