Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience.

The incidence of ductal carcinoma in situ (DCIS), a noninvasive form of breast cancer, has increased markedly in recent decades, and DCIS now accounts for approximately 20% of breast cancers diagnosed by mammography. Laboratory and patient data suggest that DCIS is a precursor lesion for invasive cancer. The appropriate classification of DCIS has provoked much debate; a number of classification systems have been developed, but there is a lack of uniformity in the diagnosis and prognostication of this disease. Further investigation of molecular markers should improve the classification of DCIS and our understanding of its relationship to invasive disease. Controversy also exists with regard to the optimal management of DCIS patients. In the past, mastectomy was the primary treatment for patients with DCIS, but as with invasive cancer, breast-conserving surgery has become the standard approach. Three randomized trials have reported a statistically significant decrease in the risk of recurrence with radiation therapy in combination with lumpectomy compared with lumpectomy alone, but there was no survival advantage with the addition of radiotherapy. Two randomized trials have suggested an additional benefit, in terms of recurrence, with the addition of adjuvant tamoxifen therapy, although in one trial the benefit was not statistically significant. Current data suggest that tamoxifen use should be restricted to patients with estrogen receptor-positive DCIS. Neither trial demonstrated a survival benefit with adjuvant tamoxifen. Ongoing and recently completed studies should provide information on outcomes in patients treated with lumpectomy alone and on the effectiveness of aromatase inhibitors as an alternative to tamoxifen.

/pdf/ductal-carcinoma-in-situ-complexities-and-challenges-3xoesyip0v.pdf

Ductal Carcinoma In Situ , Complexities and Challenges

Purpose: The increasing incidence and biological heterogeneity of ductal carcinoma in situ (DCIS) of the breast have made the management of this entity challenging and controversial. This paper rev...

Ductal Carcinoma in Situ of the Breast

Background. Ductal carcinoma in situ (DCIS) of the breast has been diagnosed increasingly since the advent of mammography. However, the natural history of these lesions remains uncertain. Ductal carcinoma in situ of the breast does not represent a single entity but a heterogeneous group with histologic and clinical differences. The histologic subtype of DCIS seems to have an influence on its biologic behavior, but there are few studies correlating subtype with biologic markers. Methods. The authors studied a consecutive series of 40 cases of DCIS and after its histologic categorization verified its relationship with ploidy using image analysis and analyzing estrogen receptor (ER), progesterone receptor (PR), p53 and c-erbB-2 expression using immunohistochemistry. Results. The three groups proposed according to the grade of malignancy were correlated significantly with some of the additional parameters studied, including aneuploidy and c-erbB-2 expression. Aneuploidy was detected in 77.5% of cases of DCIS mainly in high and intermediate grade subtypes (100% and 80% vs. 35.7% in low grade) whereas immunoreactivity for c-erbB-2 was detected in 45% of cases of DCIS mainly in the high grade group. Expression of ER and PR were observed frequently in this study (63.9% and 65.7% respectively), but without correlation with the histologic subtype of DCIS, although we found a somewhat significant association between high grade DCIS and lack of ER. p53 protein expression was detected in 36.8% of these cases, but no relationship between this expression and histologic subtype or grading of DCIS was found. Conclusions. These results provide further evidence for the morphologic and biologic heterogeneity of DCIS. Besides histologic classification and nuclear grading, some biologic markers such as aneuploidy and c-erbB-2 expression constitute additional criteria of high grade of malignancy. Cancer 1995 ; 75 :2123-31.

/pdf/ductal-carcinoma-in-situ-of-the-breast-histologic-2hyr67o0it.pdf

Ductal carcinoma in situ of the breast. Histologic categorization and its relationship to ploidy and immunohistochemical expression of hormone receptors, p53, and c-erbB-2 protein.

Human solid tumors develop multiple genetic evolutionary abnormalities as they evolve. Studies that have focused primarily on early colorectal cancer have suggested that genetic instability is a prominent feature of preinvasive disease. At least two separate mechanisms for the generation of genetic instability have been identified. The first, which involves widespread microsatellite instability in near-diploid cells, affects less than one-fifth of colon cancers. The second form of genetic instability is characterized by the development of p53 gene abnormalities that result in gross aneuploidy and multiple structural chromosomal changes. p53/aneuploidy affects most colon cancers, breast cancers, and many other solid tumors. This genetic evolutionary change commonly occurs at the interface between severe dysplasia and invasive disease. Specific post-aneuploid sequences of genetic changes that are relevant to tumor progression often involve the accumulation of multiple gain-of-function abnormalities in individual cells. The co-occurrence of Her-2/neu overexpression and EGF receptor overexpression in the same aneuploid cells defines an adeno/squamous genetic evolutionary sequence that is common to ductal breast cancers, non-small cell lung cancers, and other solid tumors. Later steps in this sequence include ras and c-myc overexpression. The neuroendocrine genetic evolutionary sequence is a separate branch of the p53/aneuploidy sequence with distinctive features that include loss of Rb and raf1 overexpression. Her-2/neu overexpression is not characteristic of this sequence; c-myc amplification/overexpression is common to both p53-associated sequences. The neuroendocrine sequence is found in small cell carcinoma of the lung and in minor proportions of other solid tumors, including breast cancer. Mutiparameter cell-based methods are especially well suited for elucidation in human solid tumors of the genetic evolutionary sequences that could provide a rational scientific basis for determining prognosis and for optimizing therapy in individual cancer patients. Cytometry 29:1–27, 1997. © 1997 Wiley-Liss, Inc.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291097-0320%2819970901%2929%3A1%3C1%3A%3AAID-CYTO1%3E3.0.CO%3B2-J

Common patterns of genetic evolution in human solid tumors

Immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA distribution patterns were assessed in 119 formalin-fixed paraffin-embedded surgical specimens of human mammary carcinomas in situ (CIS). The series consisted of 107 ductal carcinomas in situ (DCIS), 9 lobular carcinomas in situ, and 3 cases of Paget's disease of the nipple. Nuclear DNA distribution patterns were assessed by image cytometric analysis of histopathologically identified cell nuclei. Fifty-one of 107 (48%) DCIS were immunoreactive for c-erbB-2, whereas specific cell membrane staining was absent in lobular carcinomas in situ. The neoplastic cell nuclei of 46 CIS (39%) were of DNA diploid type, and 73 CIS (61%) contained aneuploid nuclear DNA. Among various histopathologic subtypes of DCIS, significant differences in c-erbB-2 immunoreactivity and nuclear ploidy were observed. DCIS of the comedo type most often were c-erbB-2 positive and exhibited aneuploid nuclear DNA histograms. DCIS of micropapillary type was the second most frequently reactive c-erbB-2 expression, and aneuploidy were less common in solid, cribriform, and papillary DCIS. The results of the current study indicate that immunohistochemical expression of the c-erbB-2 proto-oncogene product is closely related to the histopathologic subtype and the nuclear DNA content of mammary CIS. Examples of CIS that are c-erbB-2 immunoreactive and DNA aneuploid seem to have a significantly higher risk for the subsequent development of infiltrating mammary carcinoma.

Immunohistochemical c-erbB-2 protooncogene expression and nuclear DNA content in human mammary carcinoma in situ.

In contrast to the situation in invasive breast carcinoma, there are only few reports on the levels of receptors for estrogen (ER) and progesterone (PgR) in pre-invasive (in situ) breast carcinoma. In the present study ER and PgR levels were analyzed in 57 in situ human mammary carcinomas using a quatitative enzyme immunoassay method. Intraductal carcinoma was the dominating histopathological subgroup (75%). Within this subgroup the non-comedo and comedo variants comprised 66 and 34 percent respectively

Receptors for estrogen and progesterone in breast carcinoma in situ.

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Immunohistochemical c-erbB-2 protooncogene expression and nuclear DNA content in human mammary carcinoma in situ.

Receptors for estrogen and progesterone in breast carcinoma in situ.