Ductal Carcinoma In Situ of the Breast: Frequency of Biomarkers According to Histologic Subtype
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Ductal carcinoma in situ of the breast (DCIS) was studied for frequency of biologic markers. Sections were immunostained for the presence of estrogen receptor (ER), progesterone receptor (PR), c-erbB-2, epidermal growth factor receptor (EGFR), cathepsin D, and p53 with the TechMate automated immunostainer, using an avidin-biotin technique and microwave antigen retrieval. Feulgen-stained and immunostained sections were assayed for DNA ploidy and for proliferative activity (MIB-1) and angiogenesis (Factor VIII-related antigen [FVIII), respectively, using the CAS 200 image cytometer. Of the 74 DCIS, 22% were comedocarcinomas, 10% high grade, and 18% nuclear poorly differentiated. ER was present in 72%, PR in 86%, c-erbB-2 in 34%, EGFR in 0%, cathepsin D in 43%, and p53 in 57%. Sixty-five percent were aneuploid and 65% had proliferative activity (mean, <9% MIB-1); 58% had angiogenesis (mean, <6.2% FVIII). There was no significant difference in frequencies of any of these parameters according to classification except for aneuploidy and nuclear differentiation (p = 0.04). Eighty-seven percent were treated by modified radical mastectomy and 13% by local resection only. In a 6.2-year mean follow-up after mastectomy (range, 1 month to 9 years), there were no recurrences or deaths due to disease. Longer follow-up after mastectomy and follow-up of patients after lumpectomy with and without radiation is warranted.Keywords:
Progesterone receptor
Lumpectomy
Carcinoma in situ
Carcinoma in situ
Grading (engineering)
Lobular carcinoma
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Carcinoma in situ
Grading (engineering)
Lobular carcinoma
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Statistics from the Connecticut Tumor Registry from 1979 to 1988 were examined, and individual medical records from 1979 to 1983 were also reviewed. Three hundred nineteen medical records were available for review, documenting 220 cases of ductal carcinoma in situ and 102 cases of lobular carcinoma in situ. In 1979, there were 33 new cases of ductal carcinoma in situ reported to the Connecticut Tumor Registry, representing 1.8% of all breast cancers. There has been a yearly increase in ductal carcinoma in situ, with 200 new cases, or 7.4% of all breast cancers, reported in 1988. Forty-eight (22%) of 217 patients with ductal carcinoma in situ had bilateral breast involvement with ductal carcinoma in situ or an invasive breast cancer. Ten (83%) of 12 mastectomy specimens from patients with ductal carcinoma in situ who presented with nipple discharge demonstrated residual tumor, suggesting a more diffuse involvement. Two of the three reported recurrences involved nipple discharge. Thirty-seven (16.8%) of the 220 patients with ductal carcinoma in situ and six (5.9%) of the 102 patients with lobular carcinoma in situ were diagnosed as having another unrelated cancer. Ongoing clinical trials will direct optimum therapy for patients increasingly diagnosed as having ductal carcinoma in situ.
Lobular carcinoma
Carcinoma in situ
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Current data on the surgical management of breast carcinoma support the selective use of conservative surgery, ie, lumpectomy, axillary sampling, plus irradiation, rather than modified radical mastectomy. An economic comparison of these two forms of surgical therapy was conducted. Total charges for treatment (hospital and physician) of 79 patients with stage I or II breast cancer at our hospital during 1983 and 1984 utilizing either therapy demonstrated that mean total charges per patient for lumpectomy (N = 49) were $14,176 +/- $4262, and for mastectomy (N = 30) were $10,345 +/- $3134. Although hospital inpatient fees were significantly less for lumpectomy ($5741) than for mastectomy ($7328), mean total physician fees were significantly higher for lumpectomy ($4505). Radiotherapist fees and the substantial radiation therapy hospital outpatient charge for lumpectomy ($5015) made the mean total charges for lumpectomy significantly higher than for mastectomy.
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Total Mastectomy
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We have illustrated intraductal papillomas that have a variety of alterations not found in "ordinary" or typical papillomas. Many of these changes are indistinguishable from ductal carcinoma in situ. A priori, one might expect that patients with papillomas associated with changes identical to ductal carcinoma in situ would be at an increased risk for subsequent invasive carcinoma. We suspect that there is an increased risk based on the fact that seven of our 26 cases (27 percent) had fully diagnostic ductal carcinoma in situ or invasive carcinoma in the breast. However, the degree of increased risk has not been definitely established.
Carcinoma in situ
Intraductal papilloma
Atypical Hyperplasia
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Ductal carcinoma in situ develops in the milk ducts without invading the surrounding connective tissue. Progression to invasive carcinoma is slow and infrequent and is thus difficult to predict. Screening mammography has increased the number of women diagnosed with early-stage ductal carcinoma in situ. What is the best management strategy for patients whose breast biopsy suggests ductal carcinoma in situ? Is watchful waiting a reasonable option? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. Surgical resection is usually proposed to women with ductal carcinoma in situ but has not been compared with watchful waiting. Resection does not appear to have a major impact on mortality: trials of screening mammography showed no major reduction in breast cancer mortality, but screening does increase the number of diagnoses of ductal carcinoma in situ and, thus, the number of women who undergo surgery. When ductal carcinoma in situ is diagnosed by biopsy, histological examination of the surgically resected tumour reveals invasive breast cancer in about 13% to 24% of cases. Surgical removal of the tumour is usually proposed to women with ductal carcinoma in situ. Excision may be either localised (lumpectomy) or extensive (mastectomy). We found no randomised trials comparing the two approaches. Lumpectomy is usually proposed when the tumour is small (less than 20 mm) and appears to be amenable to complete excision with acceptable cosmetic results. A follow-up study of nearly 2000 women showed a recurrence rate of about 27% between 8 and 10 years after lumpectomy without further treatment. Mastectomy is usually proposed when the tumour appears to be extensive on mammography, or when complete resection with acceptable cosmetic results does not appear feasible, or when the patient chooses this option. Following mastectomy, the risk of carcinoma is similar to that of the general female population. Mastectomy and lumpectomy can both result in persistent pain, which is severe in about 13% of women. Systematic reviews of data for more than 10 000 women have shown that the following factors are statistically associated with an increased risk of recurrence after lumpectomy: age less than 50 years at diagnosis, tumours larger than 25 mm, high-grade tumours, and comedo-type necrosis. Healthy surgical margins of at least 2 mm are associated with a lower risk of recurrence. The impact of radiation therapy after lumpectomy for ductal carcinoma in situ has been evaluated in four randomised trials including a total of 3925 women. Radiation therapy reduced the risk of recurrence but did not prevent death from breast cancer. Irradiation carries a risk of skin burns and long-term cardiovascular and pulmonary toxicity. It also increases the risk of persistent post-surgical pain. In two randomised placebo-controlled trials of lumpectomy with or without radiation therapy for ductal carcinoma in situ, tamoxifen (an antiestrogen) did not affect either overall or breast cancer mortality, but it reduced the risk of recurrence by about one-quarter. Adverse effects of tamoxifen include venous thrombosis and pulmonary embolism, and endometrial cancer. In practice, women diagnosed with ductal carcinoma in situ have a number of options, none of which seems to have a clearly superior harm-benefit balance. Surgical excision reduces the risk of progression but can lead to persistent pain. Following radical mastectomy, the risk of breast cancer is similar to that of the general population. Lumpectomy is associated with a higher risk of recurrence and thus requires closer monitoring. Radiation therapy reduces the risk of recurrence in high-risk situations but has noteworthy adverse effects. Simple clinical monitoring is a valid option for asymptomatic patients: it carries a risk of progression to invasive cancer but avoids exposing many women to the adverse effects of surgery and radiation therapy.
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Watchful waiting
Carcinoma in situ
Lobular carcinoma
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The diagnosis of invasive breast cancer is most commonly made on image-guided core biopsy (CB). The presence of extensive intraductal component (EIC), as identified on subsequent lumpectomy, is associated with an increased risk of positive margins and need for further surgery. CBs demonstrating invasive breast cancer may also contain ductal carcinoma in situ (DCIS), although the significance of this finding is unclear. The objective of this study was to examine the implications of DCIS found in the original CB, specifically related to the risk of EIC and/or positive lumpectomy margins.All patients at a single academic institution who underwent initial breast conserving surgery for invasive breast cancer diagnosed on image-guided CB between 05/00 and 04/02 were included in the study. A systematic, blinded review of all CB and lumpectomy specimens was performed using standardized criteria for DCIS, EIC, and margins.A total of 95 patients were included in the study, with a mean of 5 (median 5) CB/patient. Of these, 43 (45%) patients had DCIS identified in their CB; in 34 (79%) of these patients, the DCIS was mixed with the invasive cancer. No differences in tumor size or lumpectomy volume were identified between patients with or without DCIS on CB. However, patients with DCIS were noted to be significantly younger. Overall, EIC was identified in 13 (14%) patients; the risk of EIC was significantly higher in patients with DCIS identified in CB than in those with invasive carcinoma alone (30% vs. 0%, respectively; P < 0.0001). Expectedly, the incidence of positive margins on lumpectomy was higher in patients with EIC (38% vs. 16%; P = 0.05). A trend, although not statistically significant, towards positive margins was also noted in patients with DCIS on CB compared to those with invasive carcinoma alone (24% vs. 15%, P = 0.3).The identification of DCIS in conjunction with invasive cancer on CB appears important; the absence of DCIS in a CB sample excludes the possibility of eventually identifying EIC. Knowledge of DCIS in CBs with invasive carcinoma may be helpful for surgeons in planning gross resection margins at lumpectomy.
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Carcinoma in situ
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When there is extensive breast cancer, patients typically undergo mastectomy. However, lumpectomy may still be performed for patients who are motivated to avoid a mastectomy and understand the risk for positive margins requiring second surgery in unique cases. This report details the surgical management and clinical reasoning behind lumpectomy for a multicentric breast cancer spanning 5 cm. The lumpectomy was a success with negative margins on final pathology.
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Lumpectomy
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