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Chapter 11

residual DCIS was significantly greater if the original mar- gins were positive, 43% of those with initially negative mar- gins had carcinoma in the reexcision. There was also a higher risk (76%) for residual DCIS if the primary focus was 2.5 cm or larger, but residual carcinoma was present in 57% of re- excisions for lesions smaller than 2.5 cm. Goldstein et al. 426 analyzed the quantitative relationship between the amount of DCIS in a lumpectomy and in the subsequent reexcision. The study was based on 98 patients who had a reexcision performed after a lumpectomy for DCIS. Residual DCIS was present in 52 reexcision specimens (53%). Features that were significantly related to finding DCIS in the reexcision were multifocal involvement of margins by DCIS or by DCIS ex- tending into TDLUs and extensive DCIS represented by the number of slides with the lesion. When DCIS was limited to one or two slides in the initial excision, no DCIS was detected in 62% of reexcisions, whereas DCIS was present in 100% of excisions after initial biopsies with DCIS in more than six slides. It must be reemphasized that methods for the quantita- tion of DCIS are imprecise. No method for measuring the size of DCIS has gained wide acceptance. Lagios 267 has ob- served that “quantitation, or better, estimating the extent of DCIS, should be a collaborative exercise between mam- mographer and pathologist, but is more a fictional practice than a reliable fact.” For this and other reasons summarized by Schnitt et al., 427 classifications proposed to determine the treatment of DCIS such as the VNPI, which depend on and offer precise size categories, may be viewed, at best, as gen- eral guidelines rather than as strict criteria for making thera- peutic decisions. Axillary dissection is not indicated in the majority of pa- tients with DCIS. 428 Some low ALNs may be taken with the axillary tail of the breast in the course of a mastectomy. If the lesion is extensive, DCIS, especially comedo type with marked duct distortion, it would be prudent to perform SLN mapping because of concern for undetected invasion. Mi- crometastases were detected in axillary SLNs from 4 (4.6%) of 87 patients with DCIS studied by Haigh and Giuliano 429 and in 11 (7.3%) of 150 patients reported by Cox et al. 430 As noted by Haigh and Giuliano, 429 “if metastases are detected, microinvasion can be assumed.” Treatment for the majority of patients with microinvasive duct carcinoma previously described in the literature has been mastectomy, as discussed earlier in this chapter. The outcome overall was relatively favorable after mastectomy, but the studies were not directly comparable because of dif- fering criteria for defining microinvasion. Patients treated by breast conservation therapy were described in several re- ports with results indicating that this was equally as effective as mastectomy. These and other published reports indicate that the presence of microinvasion, as variously defined in the past or as currently described in the TNM staging sys- tem (T1 mic ), probably has little independent impact on the effectiveness of conservation for local control in the breast. The characteristics of the DCIS that are associated with microinvasion, such as high grade, the presence of necro- sis, and lesion size, are crucial determinants for treatment.

The significance of multiple microinvasive foci is yet to be determined. The finding of microinvasion will lead to ALN staging, often by SLN mapping, in many patients prior to consideration of systemic therapy. 430 Advances in the understanding of molecular biology of breast carcinoma progression and the development of novel pathway-specific targeted therapy has led to the emergence of molecular-based individually tailored treatment planning for invasive breast carcinoma. Increasing understanding of molecular pathobiology of breast carcinoma progression underlies the potential of molecular-based “tailored” ther- apy. 431 Thus far, such advances have not affected the practi- cal management of DCIS. However, the routine testing of ER and PR, as well as the emerging adoption of HER2 and gene signature testing, herald the emergence of such a thera- peutic approach for DCIS. 432 Novel approaches for the management of DCIS are un- der investigation. As hypothesized by Espina and Liotta, “the survival of DCIS cells in the hypoxic, nutrient-dependent in- traductal niche could promote genetic instability and the de- repression of the invasive phenotype.” Thus, “understanding of potential survival mechanisms, such as autophagy, which might be functioning in DCIS lesions, provides strategies for arresting invasion at the premalignant stage.” 433 The poten- tial utility of ductoscopy in detecting occult intraductal le- sions, and of ductoscopically guided lumpectomy, is under investigation and could potentially lead to more targeted lumpectomy procedures. 434 The treatment of DCIS continues to evolve 435 and, in at least a proportion of cases, remains a “conundrum.” 436 It is likely that various nomograms 415 andmolecular marker stud- ies 437 will assume an increasingly significant role in its man- agement. Advances in various forms of radiologic screening, and refinements therein, will likely optimize the detection of DCIS, that is, breast carcinoma in its earliest form. 438,439 REFERENCES 1. Broders AC. Carcinoma in situ contrasted with benign penetrating epithelium. JAMA 1932;99:1670–1674. 2. Warren JC. Abnormal involution of the mammary gland with its treatment by operation. Am J Med Sci 1907;134:521–535. 3. Cheatle GL. Cysts and primary cancer in cysts of the breast. Br J Surg 1920–1921;8:149–166. 4. Bloodgood JC. The pathology of chronic cystic mastitis of the female breast. Arch Surg 1921;3:445–542. 5. Bloodgood JC. Border-line breast tumors. Ann Surg 1931;93:235–249. 6. Muir R. The evolution of carcinoma of the mamma. J Pathol Bacteriol 1941;52:155–172. 7. Schultz-Brauns O. Die geschwulste der Brustbrüse. In: Henke F, Lubarsch O, eds. Handbuch der speziellen Pathologischen Anatomie und Histologie, VII . Berlin: Verlag von Julius Springer, 1933. 8. Bloodgood JC. Comedo carcinoma or comedo-adenoma of the female breast. Am J Cancer 1934;22:842–853. 9. Lewis D, Geschickter CF. Comedocarcinoma of the breast. Arch Surg 1938;36:225–244. 10. Cheatle GL, Cutler M. Tumors of the breast. Their pathology, symp- toms, diagnosis, and treatment. Philadelphia: JB Lippincott, 1931. 11. Fechner RE. One century of mammary carcinoma in situ . What have we learned? Am J Clin Pathol 1993;100:654–661. 12. Farante G, Zurrida S, Galimberti V, et al. The management of ductal intraepithelial neoplasia (DIN): open controversies and guidelines of