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.

Interventional oncology in the elderly: complications and early response in liver and kidney malignancies.

OBJECTIVES: The complication rate, loco-regional responses and length of hospital stay were analyzed in patients with liver and kidney cancer older than 70years treated with interventional oncology procedures. The findings from the older population were compared with the younger patients (<70years) to detect any difference not related to chance. MATERIALS AND METHODS: Prospectively collected data on patients who underwent hepatic artery embolization (with or without radiofrequency ablation) and kidney radiofrequency ablation were retrospectively analyzed. Complication rates, loco-regional responses and length of hospital stay for patients older and younger than 70 were compared. RESULTS: 163 patients were treated, 66 (40.5%) older and 97 (59.5%) younger than 70years. The complication rate in patients older than 70 was 4.5% (3/66 pts) versus 3.1% (3/97 pts) (p=0.69) in the younger age-group. The complication rates for the liver embolization group, liver embolization plus radiofrequency and kidney radiofrequency group were 2/90 pts (2.2%), 2/42 pts (4.8%) and 2/31 pts (6.5%), respectively (p=0.46). Median hospital stay was three nights in both older and younger patients. Response rates were not significantly influenced by age. CONCLUSION: Liver embolization with or without radiofrequency and renal radiofrequency are safe and effective in older patients. Age alone should not be considered a contraindication to treatment in carefully selected patients.

High Ki67 predicts unfavourable outcomes in early breast cancer patients with a clinically clear axilla who do not receive axillary dissection or axillary radiotherapy.

AIM: Axillary dissection is increasingly forgone in early breast cancer patients with a clinically negative axilla. The GRISO 053 randomised trial recruited 435 patients of age over 45 years, tumour ≤1.4 cm and clinically negative axilla, to assess the importance of axillary radiotherapy versus no axillary radiotherapy in patients not given axillary dissection. In the present study on a subgroup GRISO cases our aim was to assess the prognostic importance of tumour biological factors after more than 10 years of follow-up. METHODS: We retrospectively assessed biological factors in a subgroup of 285 GRISO cases (145 given axillary radiotherapy; 140 not given axillary radiotherapy) with complete biologic, therapeutic and follow-up information, using multivariable Cox proportional hazards regression modelling. RESULTS: Only 10-year cumulative incidence of distant metastasis was lower in the axillary radiotherapy (1%) than no axillary radiotherapy arm (7%) (p=0.037). Irrespective of study arm, hormone receptor positivity had significantly favourable effects on 10-year disease-free survival (DFS) and overall survival. human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes were associated with lower 10-year DFS (60% and 76%, respectively) than luminal A (96%) and B (91%) (p=0.001). Ten-year DFS for high (≥14%) Ki67 cancers was lower than for low Ki67 cancers (p=0.027); however, this effect was mainly confined to the no axillary radiotherapy arm. CONCLUDING STATEMENT: For patients with clinically node-negative small breast cancer not given axillary dissection, 10-year DFS is worsened by HER2 positivity, triple-negative phenotype and high Ki67. Axillary radiotherapy counteracts the negative prognostic effect of high Ki67 in patients not receiving axillary dissection.

Tailoring treatment for ductal intraepithelial neoplasia of the breast according to Ki-67 and molecular phenotype.

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.

Analysis of local and regional recurrences in breast cancer after conservative surgery.

BACKGROUND: A minority of patients treated conservatively for breast cancer will develop local or regional recurrences. Our aim was to determine how their occurrence may be linked to the evolution of the disease. PATIENTS AND METHODS: We analyzed 2784 women treated for early-stage breast cancer by quadrantectomy and whole-breast irradiation in a single institution. We evaluated the prognostic factors associated with local, regional and distant recurrences and the prognostic value of local and regional recurrences on systemic progression. RESULTS: After a median follow-up of 72 months, we observed 33 local events, 35 regional events and 222 metastases or deaths as first events (5-year cumulative incidence 1.1%, 1.2% and 7.6%, respectively). Size, estrogen receptor status, Her2/Neu and Ki-67 were associated with all three types of events, while axillary status and vascular invasion were associated only with the occurrence of metastases or death. Young age increased the risk of local recurrence. Local and regional recurrences were associated with an increased risk of systemic progression: hazard ratios 2.5 [95% confidence interval (CI) 1.1-5.8] and 5.3 (95% CI 3.0-9.5), respectively. CONCLUSIONS: Local and regional recurrences after breast-conserving surgery are rare events. They are markers of tumor aggressiveness and indicators of an increased likelihood of distant metastases.