Gabriel Farante

Preoperative staging of primary breast cancer. A multicentric study.

This article reports on a consecutive series of 3627 breast cancer (BC) patients undergoing preoperative staging by chest x‐ray (CXR), bone x‐ray (BXR) or bone scintigraphy (BS), and liver ecography (LE) or liver scintigraphy (LS). The detection rate (DR) of preclinical asymptomatic distant metastases depended on the T and N category (TNM classification system), and was very low (CXR: 0.30%, BXR: 0.64%, BS: 0.90%, LE: 0.24%, LS: 0.23%). The sensitivity, determined after a 6‐month follow‐up, was below 0.50% for all tests. The highest value (0.48%) was recorded for BS, which also had the lowest specificity (0.95%). The entire preoperative staging policy using the studied tests seems questionable due to poor sensitivity and an extremely low DR of distant metastases.

A new option for early breast cancer patients previously irradiated for Hodgkin's disease: intraoperative radiotherapy with electrons (ELIOT)

IntroductionPatients who have undergone mantle radiotherapy for Hodgkins disease (HD) are at increased risk of developing breast cancer. In such patients, breast conserving surgery (BCS) followed by breast irradiation is generally considered contraindicated owing to the high cumulative radiation dose. Mastectomy is therefore recommended as the first option treatment in these women.MethodsSix patients affected by early breast cancer previously treated with mantle radiation for HD underwent BCS associated with full-dose intraoperative radiotherapy with electrons (ELIOT).ResultsA total dose of 21 Gy (prescribed at 90% isodose) in five cases and 17 Gy (at 100% isodose) in one case were delivered directly to the mammary gland without acute complications and with good cosmetic results. After an average of 30.8 months of follow up, no late sequelae were observed and the patients are free of disease.ConclusionIn patients previously irradiated for HD, ELIOT can avoid repeat irradiation of the whole breast, permit BCS and decrease the number of avoidable mastectomies.

The clinical relevance of micropapillary carcinoma of the breast: a case–control study

To ascertain the prognostic relevance of micropapillary carcinoma, a specific type of breast tumour.

No more axillary dissection in patients with ductal intraepithelial neoplasia (DIN)

Although it has been shown that axillary dissection (AD) is unnecessary and without a rational basis in patients with pure ductal intraepithelial neoplasia (DIN), it is evident from the literature that AD (i.e., in the USA and in the UK) has been still recently performed. Furthermore sentinel lymph node biopsy (SLNB) is not usually required in all cases of DIN, but may be indicated in certain specific cases. Even if the SLNB is positive, AD should not be performed immediately but only in cases where an invasive component is found on definitive pathological examination of the DIN lesions.

Are all patients with ductal carcinoma in situ of the breast candidates for radiotherapy after breast conservative treatment? Institute of European Oncology Guidelines.

To the Editor: At present, we know that adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) reduces local recurrence (LR) rates by about 50% in patients with ductal carcinoma in situ (DCIS) of the breast, with no benefits on survival. Comparable reductions were seen for the rise of both invasive and noninvasive LR. Also, nonsignificant long-term toxicity from RT was found (1). This has been demonstrated by wellknown randomized trials as NSABP B-17 (2), UK-ANZ (3), EORTC 10853 (4), SweDCIS (5), and recently confirmed by an update of the same studies (6). But do all DCIS patients have to undergo RT after BCS? This question was answered with opposing opinions by Buchholz (positively) (7) and Silverstein (negatively) (8). The answer offered by the 2011 St Gallen Consensus Conference (9) was in the negative: most panelists considered that RT could be avoided in elderly women or in patients with low-grade DCIS and clearly negative margins. On this last point, there is no agreement about the limits of safety related to the width of surgical margins (10) that vary from 10 mm to 1 mm, with intermediate measures of 3 mm, 2–3 mm and 2 mm. On the other hand, DCIS patients with G3 disease and necrosis are generally considered suitable for adjuvant RT, as both of them are associated with higher risk of recurrence (11). Major controversies are related to the need for RT in lower grade disease. Two prospective studies showed contradictory results: in the Dana-Faber Cancer Institute trial the omission of RT resulted in a cumulative LR rate of 12% at 5-year (12). Conversely, the EORTC 10850 trial showed a reduced risk of LR rate in the G1 subgroup after surgery alone, less than 10%, but at a doubled follow-up time, 10 years (4). Advances in molecular profiling analysis (13) along with the well-known clinical and pathologic parameters might help to improve risk stratification and decision-making. Several studies have investigated the prognostic significance of biomarkers, such as estrogen receptor status, HER2/neu expression, Ki-67-expression (14), but their validation is complex and needs to be tested prospectively in large cohorts of patients. These previous data justify the still open debate regarding the practice of RT in patients with DCIS. The lack of shared opinions is confirmed if we examine the published surveys on the indications and utilization of RT after BCS. In the UK, patients were significantly more likely to have RT planned (and administered) if they had large (>15 mm), intermediate or high-grade tumors or if central comedo-type necrosis was present (15). In North America, there were strong correlations between the grade of DCIS and margin status and the use of RT (16). Recommendations are in favor of RT as grade increased (more than 97% in G3) and margin width decreased (more than 95% with <10 mm). There were substantial differences in opinion between North America and Europe, as well as in Europe itself, especially regarding low-grade and wide margin lesions, for which Europeans offered observations more often than Americans (56.9% versus 41.2%). Substantial differences by surgeons in surgical treatment, receipt of RT and margin status found by Dick et al. (17) emphasize the importance of the physicians in the quality of care of DCIS. The heterogeneity of the disease accounts for the heterogeneity of treatment and makes the perception of risk and the treatment choices challenging (18). At the European Institute of Oncology (IEO), in Milan, for more than a decade RT was only administered to DCIS patients with G3, or G2 with comedo-type Address correspondence and reprint requests to: Gabriel Farante, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy, or e-mail: gabriel.farante@ieo.it

Ipsilateral Breast Tumor Reappearance and Contralateral Breast Cancer after Primary Breast Cancer Treatment: A Comprehensive Retrospective Study of 15,168 Patients

Objective: The aim of this retrospective study was to assess the risk factors for developing ipsilateral breast tumor reappearance (IBTR) and de novo contralateral breast cancer (BC) after primary BC treatment. Methods: Retrospectively, 15,168 consecutive patients with primary monolateral BC were enrolled in this monocentric study (from June 1994 to December 2006). Clinicopathological features, follow-up, and survival at 15 years were considered for statistical analysis. Results: Significant associations of increased risk for IBTR were verified with metastatic axillary lymph nodes (HR 1.37 [1.15–1.62], p = 0.0004), high tumor grade G2 (HR 1.35 [1.05–1.74], p = 0.02) and G3 (HR 1.35 [1.01–1.79], p = 0.04), luminal B (HR 1.51 [1.25–1.82], p < 0.0001), and HER2-positive (HR1.66 [1.14–2.41], p = 0.008) and triple-negative subtype (HR 1.54 [1.07–2.21], p = 0.02). Older age (HR 1.44 [1.08–1.91], p = 0.01) and positive family history (HR 1.85 [1.47–2.32], p < 0.0001) were risk factors for contralateral BC. Significant protective factors for IBTR were hormonotherapy (HR 0.71 [0.59–0.85], p = 0.0003), chemotherapy (HR 0.72 [0.60–0.87], p = 0.001), and radiotherapy (HR 0.73 [0.61–0.87], p = 0.0005). Hormonotherapy was also confirmed as a protective factor for contralateral second BC (HR 0.43 [0.30–0.60], p < 0.0001). Conclusions: We classified factors for IBTR and contralateral BC in high- and low-risk groups. In the high-risk group, breast surgery still remains more important than in the low-risk group, which seems to benefit more from adjuvant treatments.

120 P - Chemoprevention of breast cancer: update of the Italian trial in hysterectomised women

Three major studies are ongoing in the U.K., the U.S.A. and Italy in order to verify the efficacy of Tamoxifen to Inhibit or reverse breast carcinogenesis and to evaluate the risk/benefit ratio of its use in healthy women. The 3 studies are similar: double blind, randomised trials with Tamoxifen (20 mg/day) versus placebo, in healthy women, aged 35 to 70. The main difference with the Italian Study is in the target population, which is hysterectomised women only. As of December 31,1995 the Italian trial is run by 48 centers, under the coordination of the European Institute of Oncology in Milan, end the accrual has reached 4.320 subjects. Their median age is 51 and 18% of them have at least one first degree relative affected by breast cancer. Sixteen percent of the enrolled women are using estrogen replacement therapy, which is not a cause of exclusion in our study. We had 63% of the participants with some side-effects. which have been mainly of moderate intensity and especially menopausal symptoms like hot flushes and vaginal dryness. Twentyeight cases of phlebitis were reported, of which 3 assessed as deep venous thrombophlebitis. The number of drop-outs, so far, is reasonably low (15.9%). Thirtyone cases of cancer have been reported, including fourteen breast cancers. The Italian study is showing the feasibililty to run these chemoprevention trials in hysterectomised women, thus avoiding the risk of endometrial cancer, which seems to be the major side-effect of Tamoxifen.

130 P - Breast conservation without axillary dissection

Starting from the evidence that surgical treatment of the axilla does not in itself improve the survival of patients with small size breast cancer (