Fisher, B. et al. Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience. Semin. Oncol. 28, 400-418

National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA.
Seminars in Oncology (Impact Factor: 3.94). 09/2001; 28(4):400-18. DOI: 10.1053/sonc.2001.26151
Source: PubMed

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.

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    • "In the French and International studies [20] [48], the LR rates in women over 60 years were 8% and 5% after local excision + PORT, with 84-and 120-month follow-ups, respectively. In NSABP B-17 and Houston series, the rates in women over 70 were 9% and 2%, with 90-and 60-month follow-ups respectively [14] [35] [47]. A retrospective analysis of SEER data including 3409 women over 66 treated by BCS for DCIS between 1992 and 1999 [52] showed that PORT lowered local recurrence risk with a HR = 0.32 (95% CI: 0.24–0.44). "
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    ABSTRACT: Often considered an “indolent” disease for which a treatment de-escalation is advocated, ductal carcinoma in situ (DCIS) of the breast has been recently shown to be associated with a significant increase in long-term mortality in case of invasive local recurrence (LR). The publication of data from four randomised trials did not prevent the continuation of the debates about the pros and cons of postoperative radiation therapy (PORT) for optimal DCIS management. Actually only partial answers regarding the impact of PORT on local control had been brought by these randomised trials among others due to differences in pathological assessment among these controlled studies. A biologically heterogeneous disease, DCIS is characterised by a large variation in clinical behaviour, which hampers the identification of those patients for whom PORT might be considered as an overtreatment. At the light of the most recent biological and clinical studies, this review tries to identify accurately the LR risks associated with both tumour- and patient-related factors and to analyse the treatment-related parameters impacting significantly on the patient outcome.
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    • "On the other hand, RT was recommended to women with DIN2–DIN3 disease with a combination of risk factors such as young age, the presence of comedo histology or necrosis, and positive margins. Given the results of randomised trials confirming a beneficial effect of RT (Fisher et al, 2001; Bijker et al, 2006), physicians' recommendations towards RT have changed over time. The most common RT schedule was 50 Gy without a boost. "
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    ABSTRACT: Background: The post-surgical management of ductal intraepithelial neoplasia (DIN) of the breast is still a dilemma. Ki-67 labelling index (LI) has been proposed as an independent predictive and prognostic factor in early breast cancer. Methods: The prognostic and predictive roles of Ki-67 LI were evaluated with a multivariable Cox regression model in a cohort of 1171 consecutive patients operated for DIN in a single institution from 1997 to 2007. Results: Radiotherapy (RT) was protective in subjects with DIN with Ki-67 LI ≥14%, whereas no evidence of benefit was seen for Ki-67 LI <14%, irrespective of nuclear grade and presence of necrosis. Notably, the higher the Ki-67 LI, the stronger the effect of RT (P-interaction <0.01). Hormonal therapy (HT) was effective in both Luminal A (adjusted hazard ratio (HR)=0.56 (95% CI, 0.33–0.97)) and Luminal B/Her2neg DIN (HR 0.51 (95% CI, 0.27–0.95)). Conclusion: Our data suggest that Ki-67 LI may be a useful prognostic and predictive adjunct in DIN patients. The Ki-67 LI of 14% could be a potential cutoff for better categorising this population of women at increased risk for breast cancer and in which adjuvant treatment (RT, HT) should be differently addressed, independent of histological grade and presence of necrosis.
    British Journal of Cancer 04/2013; 108(8). DOI:10.1038/bjc.2013.147 · 4.82 Impact Factor
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    • "A 2 × 2 factorial design was used in the fourth study; the aim was to see the effectiveness of either adjuvant RT or hormonal therapy with Tamoxifen (TAM); allocation of patients could have happened for both treatments (RT and TAM) or just for one of the two, reserving the second as the only other choice. The first study, the American NSABP-B-17 trial [16], randomized 818 cases of DCIS, between October 1985 and December 1990, 80.4% of which mammographically diagnosed (Table 1). "
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    ABSTRACT: Several large prospective and retrospective studies have demonstrated excellent long-term outcomes after breast conservative treatment with radiation in invasive breast cancer. Breast-conserving surgery (BCS) followed by radiotherapy (RT) is an accepted management strategy for patients with DCIS. Adding radiation treatment after conservative surgery enables to reduce, without any significant risks, the rate of local recurrence (LR) by approximately 50% in retrospective and randomized clinical trials. As about 50% of LRs are invasive and have a negative psychological impact, minimizing recurrence is important. Local and local-regional recurrences after initial breast conservation treatment with radiation can be salvaged with high rates of survival and freedom from distant metastases.
    05/2012; 2012:635404. DOI:10.1155/2012/635404
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