Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience.
ABSTRACT The National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted two sequential randomized clinical trials to aid in resolving uncertainty about the treatment of women with small, localized, mammographically detected ductal carcinoma in situ (DCIS). After removal of the tumor and normal breast tissue so that specimen margins were histologically tumor-free (lumpectomy), 818 patients in the B-17 trial were randomly assigned to receive either radiation therapy to the ipsilateral breast or no radiation therapy. B-24, the second study, which involved 1,804 women, tested the hypothesis that, in DCIS patients with or without positive tumor specimen margins, lumpectomy, radiation, and tamoxifen (TAM) would be more effective than lumpectomy, radiation, and placebo in preventing invasive and noninvasive ipsilateral breast tumor recurrences (IBTRs), contralateral breast tumors (CBTs), and tumors at metastatic sites. The findings in this report continue to demonstrate through 12 years of follow-up that radiation after lumpectomy reduces the incidence rate of all IBTRs by 58%. They also demonstrate that the administration of TAM after lumpectomy and radiation therapy results in a significant decrease in the rate of all breast cancer events, particularly in invasive cancer. The findings from the B-17 and B-24 studies are related to those from the NSABP prevention (P-1) trial, which demonstrated a 50% reduction in the risk of invasive cancer in women with a history of atypical ductal hyperplasia (ADH) or lobular carcinoma in situ (LCIS) and a reduction in the incidence of both DCIS and LCIS in women without a history of those tumors. The B-17 findings demonstrated that patients treated with lumpectomy alone were at greater risk for invasive cancer than were women in P-1 who had a history of ADH or LCIS and who received no radiation therapy or TAM. Although women who received radiation benefited from that therapy, they remained at higher risk for invasive cancer than women in P-1 who had a history of LCIS and who received placebo or TAM. Thus, if it is accepted from the P-1 findings that women at increased risk for invasive cancer are candidates for an intervention such as TAM, then it would seem that women with a history of DCIS should also be considered for such therapy in addition to radiation therapy. That statement does not imply that, as a result of the findings presented here, all DCIS patients should receive radiation and TAM. It does suggest, however, that, in the treatment of DCIS, the appropriate use of current and better therapeutic agents that become available could diminish the significance of breast cancer as a public health problem.
SourceAvailable from: Melvin J Silverstein[Show abstract] [Hide abstract]
ABSTRACT: The University of Southern California/Van Nuys Prognostic Index (USC/VNPI) is an algorithm that quantifies five measurable prognostic factors known to be important in predicting local recurrence in conservatively treated patients with ductal carcinoma in situ (DCIS) (tumor size, margin width, nuclear grade, age, and comedonecrosis). With five times as many patients since originally developed, sufficient numbers now exist for analysis by individual scores rather than groups of scores. To achieve a local recurrence rate of less than 20% at 12 years, these data support excision alone for all patients scoring 4, 5, or 6 and patients who score 7 but have margin widths ≥3 mm. Excision plus RT achieves the less than 20% local recurrence threshold at 12 years for patients who score 7 and have margins <3 mm, patients who score 8 and have margins ≥3 mm, and for patients who score 9 and have margins ≥5 mm. Mastectomy is required for patients who score 8 and have margins <3 mm, who score 9 and have margins <5 mm and for all patients who score 10, 11, or 12 to keep the local recurrence rate less than 20% at 12 years. DCIS is a highly favorable disease. There is no difference in mortality rate regardless of which treatment is chosen. The USC/VNPI is a numeric tool that can be used to aid the treatment decision-making process.The Breast Journal 01/2015; 21(2). DOI:10.1111/tbj.12368 · 1.43 Impact Factor
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ABSTRACT: A subset of patients with ductal carcinoma in situ (DCIS) will develop invasive breast cancer (IBC). To date, there are no effective predictive biomarkers for identifying this subset with worse prognosis whose lesions are essentially indistinguishable histologically from those with favorable outcomes. We hypothesized that measurable parameters that discriminate DCIS from DCIS with concurrent invasion may serve as diagnostic biomarkers (BM) of progressive cancer in situ (CIS). Using a novel imaging-based method of tissue testing, we measured the relative expression levels of three candidate BM proteins specifically implicated in IBC progression - the insulin-like growth factor I receptor (IGF-IR), Ras-related protein 1 (Rap1), and Vav2 oncoprotein. Protein profiles were compared in 42 histologically normal mammary epithelial samples, 71 CIS (35 without/36 with invasion either on diagnostic biopsy or final surgical excision), and 98 IBC of known estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. The levels of the IGF-IR and Rap1 protein expression were significantly elevated in ER-positive (ER+/PR+/-/HER2 -) DCIS relative to normal epithelium (P <0.0001). The IGF-IR protein expression was also significantly up regulated in HER2-positive (ER+/-/PR+/-/HER2+) DCIS relative to normal epithelium (P = 0.0002). IGF-IR and Rap1 protein expression levels were similar among DCIS patients without or with concurrent invasion. Vav2 upregulation in DCIS relative to normal group was not associated with steroid hormone receptor and HER2 status, but was associated with the presence of concurrent invasion, including microinvasion (invasive foci of less than 1 mm). DCIS with high Vav2 were more than twice as likely to progress to invasive cancers as DCIS with low Vav2 (odds ratio, 2.42; 95% CI, 1.26-4-65; P =0.008). Furthermore, a receiver operating characteristic curve analysis revealed moderate ability of Vav2 protein expression measurements in DCIS to predict the existence of invasion concurrent with DCIS (area under the curve, 0.71; 95% CI, 0.59- 0.84). Our novel findings hold promise for utilizing Vav2 protein as a predictive BM for differentiating progressive from non-progressive DCIS.11/2014; 2:22. DOI:10.1186/2050-7771-2-22
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ABSTRACT: Considerable debate exists about the optimal treatment of ductal carcinoma in situ (DCIS). Using electronic data sources, we examined first course treatment patterns among women aged 18 years and older diagnosed with DCIS between 2000-2010 from six Kaiser Permanente (KP) regions. We calculated the proportion of patients receiving breast conserving surgery (BCS), BCS plus radiation therapy, unilateral mastectomy, bilateral mastectomy, and hormone therapy. Multinomial logistic regression was used to assess the association between patient characteristics and treatment. We included 9,437 women: 1,086 (11.5%) African-American; 1,455 (15.4%) Asian; 918 (9.7%) Hispanic; and 5,978 (63.3%) non-Hispanic white. Most cases (42.2%) received BCS plus radiation as their initial treatment. Nearly equal numbers of women received BCS without radiation (28.5%) or unilateral mastectomy (24.6%). Use of bilateral mastectomy was uncommon (4.7%), and most women (72.2%) did not receive hormone therapy has part of their first course treatment. We observed statistically significant differences in treatment patterns for DCIS by KP region and patient age. Predictably, nuclear grade and the presence of comorbidities were associated with first course treatment for DCIS. We observed statistically significant increases in BCS plus radiation therapy and bilateral mastectomy over time. Although still uncommon, the frequency of bilateral mastectomy increased from 2.7% in 2000 to 7.0% in 2010. We also observed differences in treatment by race/ethnicity. Our findings help illustrate the complex nature of DCIS treatment in the United States, and highlight the need for evidence based guidelines for DCIS care.SpringerPlus 01/2015; 4:24. DOI:10.1186/s40064-014-0776-7