Risk of subsequent in situ and invasive breast cancer in human epidermal growth factor receptor 2-positive ductal carcinoma in situ.
BACKGROUND
To assess the prognostic role of human epidermal growth factor receptor 2 (HER2) overexpression in patients with ductal carcinoma in situ (DCIS).


PATIENTS AND METHODS
We identified patients with HER2-positive DCIS among a population of 1667 cases, prospectively diagnosed and surgically treated at the European Institute of Oncology from 1996 to 2008. Rates of subsequent DCIS or invasive cancer in HER2-positive disease were estimated. We evaluated Cumulative Incidence of In Situ Breast Cancer Recurrence (isBCR), INvasive Breast Cancer Recurrence (IBCR) and any Breast Cancer Recurrence (BCR). isBCR, IBCR and BCR were defined as the time from surgery to breast cancer recurrence as first event (in situ, invasive or both, respectively) or last visit in case of no events.


RESULTS
We identified 560 (33.5%) patients with HER2-positive DCIS. The median follow-up was 7.6 years (interquartile range 5.9-9.5). We observed 422 events out of 1667 patients, with 141 in situ recurrences, 201 invasive recurrences and 80 other events (64 second primaries and 16 deaths). The 10-year isBCR proportions were 11.8% [95% confidence interval (CI) 9.0% to 15.4%] in the HER2-positive group and 8.8% (95% CI 6.9% to 11.0%) in the HER2-negative group (Gray test, P = 0.010). At multivariable analysis, the adjusted risk of isBCR was higher in the HER2-positive group than in the HER2-negative group [hazard ratio (HR) HER2 positive versus negative: 1.59 (95% CI 1.06-2.39)]. We observed significant differences both in BCR and isBCR for patients treated by quadrantectomy without radiotherapy versus patients treated with radiotherapy [adjusted HR HER2 positive versus negative: 1.53 (95% CI 1.07-2.18) and adjusted HR HER2 positive versus negative: 2.18 (95% CI 2.18-3.69), respectively].


CONCLUSION
HER2 overexpression predicts an increased risk of isBCR. Radiotherapy reduces local failure rates in HER2-positive DCIS.
['Curigliano|G|G|', 'Disalvatore|D|D|', 'Esposito|A|A|', 'Pruneri|G|G|', 'Lazzeroni|M|M|', 'Guerrieri-Gonzaga|A|A|', 'Luini|A|A|', 'Orecchia|R|R|', 'Goldhirsch|A|A|', 'Rotmensz|N|N|', 'Bonanni|B|B|', 'Viale|G|G|']
D000328:Adult D000368:Aged D014408:Biomarkers, Tumor D001943:Breast Neoplasms D018270:Carcinoma, Ductal, Breast D002285:Carcinoma, Intraductal, Noninfiltrating D003131:Combined Modality Therapy D005260:Female D005500:Follow-Up Studies D006801:Humans D007124:Immunoenzyme Techniques D015994:Incidence D007558:Italy D008875:Middle Aged D060787:Neoplasm Grading D009361:Neoplasm Invasiveness D009364:Neoplasm Recurrence, Local D009367:Neoplasm Staging D011379:Prognosis D011446:Prospective Studies D018719:Receptor, ErbB-2 D011960:Receptors, Estrogen D011980:Receptors, Progesterone D012189:Retrospective Studies D012307:Risk Factors
ductal carcinoma in situ epidermal growth factor receptor 2 (HER2) overexpression