Edoardo Botteri

Repeating conservative surgery after ipsilateral breast tumor reappearance: Criteria for selecting the best candidates

BackgroundMastectomy is still considered the treatment of first choice in patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and whole-breast radiotherapy.MethodsWe retrospectively evaluated 161 patients with invasive IBTR who underwent a second BCS in order to describe prognosis, determine predictive factors of outcome, and select the subset of patients with the best local control. Median follow-up after IBTR was 81xa0months.ResultsMedian age at IBTR was 53xa0years. Five-year overall survival after IBTR was 84xa0% (95xa0% confidence interval [CI] 78–89). Five-year cumulative incidence of a second local event after IBTR was 29xa0% (95xa0% CI 22–37). At the multivariate analysis, IBTR size >2xa0cm and time to relapse ≤48xa0months significantly increased the risk of local reappearance (hazard ratio [HR] 3.3, 95xa0% CI 1.6–7.0; and HR 1.9, 95xa0% CI 1.1–3.5). The 5-year cumulative incidence of a further local reappearance of the tumor after repeating BCS was 15.2xa0% in the patients with IBTR ≤2xa0cm and time to IBTR >48xa0months, 31.2xa0% in the patients with IBTR ≤2xa0cm and time to IBTR ≤48xa0months, and 71.2xa0% in patients with IBTR >2xa0cm (Pxa0<xa00.001).ConclusionsThe best candidates for a second BCS are those with small (≤2xa0cm) and late (>48xa0months) IBTR. The information about the risk of a further local reappearance after repeating BCS should be shared with the patients in the decision making process.

Biopsy of liver metastasis for women with breast cancer: Impact on survival

BACKGROUNDnBiopsy of metastatic site of disease can influence treatment decisions, but its impact on survival remains uncertain.nnnPATIENTS AND METHODSnOne-hundred patients with first metachronous liver metastases (LM) from breast cancer (BC) who underwent liver biopsy between 1999 and 2009 were identified. One-hundred matched control patients with LM from BC and no biopsy were selected.nnnRESULTSnLiver biopsy had no statistically significant impact on survival when comparing biopsied patients to controls [HR 0.82 (95% CI 0.58-1.16)]. Patients with early metastasis (within 3 years) undergoing liver biopsy had a better survival [HR 0.60 (95% CI 0.38-0.97)] compared to those who did not. Liver biopsy had no statistically significant impact on survival in patients with late LM (after 3 years) [HR 1.09 (95% CI 0.69-1.74)]. We observed that 18 out of 100 biopsied patients (18.0%) had a conversion of predictive factors which allowed adjusting for therapy, specifically new expression of ER (n=5), overexpression of HER2 (n=12) or both (n=1). Fourteen out of 18 (77.8%) received anti-HER2 treatment for the first time at the time of metastasis and 3 others (16.7%) received hormone therapy. Those 18 patients showed a better survival compared to the other 82 biopsied patients [HR 0.55 (95% CI 0.28-1.10)] and compared to the 13 biopsied patients with disappearance of features which predicted responsiveness to a given treatment [HR 0.19 (95% CI 0.06-0.62)].nnnCONCLUSIONSnLiver biopsy can impact survival of patients with early metastases from BC. Discordance between primary and distant lesions can offer the patients new treatment options.

Primary and secondary angiosarcomas of the breast: a single institution experience

Angiosarcomas of the breast (ASB) are rare, representing <1% of breast malignancies. They can develop as a primary or secondary malignancy, also called post-radiation angiosarcoma. The aim of the this study is to discuss diagnosis, treatment, and outcome of primary and secondary ASB patients, diagnosed and treated in a single institution, over a 10-year period and to further compare the two conditions. We retrieved 28 consecutive cases of ASB, diagnosed from 1999 to 2009 at the European Institute of Oncology. Clinical and pathologic findings and survival analyses were performed. Of the 28 cases (27 women and 1 man), eight were primary breast angiosarcomas (PBA) and 20 were secondary breast angiosarcomas (SBA). Median follow-up was 23xa0months (range 1–112xa0months). Type of treatment (conservative or radical surgery) did not affect survival in both types of angiosarcomas. The clinical course observed was characterized by a high rate of local recurrence rather than distant metastasis or death from disease. There was a correlation between histological grade and prognosis of angiosarcomas with high-grade tumors presenting worse prognosis. SBA had a poorer prognosis compared to PBA. Our data indicate that primary and secondary ASB are distinct clinical and pathological features. SBA showed worse prognosis and was more often diagnosed in the study period compared to PBA. Physicians who care for patients who have been treated with radiation must be aware of its potential to induce angiosarcoma and stay vigilant in its detection.

Is [18F] fluorodeoxyglucose uptake by the primary tumor a prognostic factor in breast cancer?

BACKGROUNDnWe retrospectively investigated (18)F-FDG uptake by the primary breast tumor as a predictor for relapse and survival.nnnPATIENTS AND METHODSnWe studied 203 patients with cT1-T3N0 breast cancer. Standardized uptake value (SUVmax), was measured on the primary tumor. After a median follow-up of 68 months (range 22-80), the relation between SUVmax and tumor factors, disease free-survival (DFS) and overall survival (OS) was investigated.nnnRESULTSnIn the PET-positive patients, the median FDG uptake by the tumor was 4.7. FDG uptake was significantly related to tumor size, number of involved axillary nodes, grade, negative ER, high Ki-67 and HER2 overexpression. No distant metastases or deaths occurred in the PET-negative group. Five-year DFS was 97% and 83%, respectively in the PET-negative and PET-positive groups (P = 0.096). At univariate analysis, DFS was significantly lower in patients with SUVmax >4.7 compared to the patients with negative PET (P = 0.042), but not to the patients with SUVmax ≤4.7 (P = 0.106). At multivariable analysis, among PET-positive patients, SUVmax was not an independent prognostic factor for DFS (HR(>4.7 vs ≤4.7): 1.02 (95% CI 0.45-2.31)). Five-year OS was 100% and 93%, respectively, in the PET-negative and PET-positive groups (P = 0.126).nnnCONCLUSIONnFDG uptake by the primary lesion was significantly associated with several prognostic variables, but it was not an independent prognostic factor.

Breast cancer subtype approximations and loco-regional recurrence after immediate breast reconstruction

BACKGROUNDnA small but significant proportion of patients with breast cancer (BC) will develop loco-regional recurrence (LRR) after immediate breast reconstruction (IBR). The LRR also varies according to breast cancer subtypes and clinicopathological features.nnnMETHODSnWe studied 1742 consecutive BC patients with IBR between 1997 and 2006. According to St Gallen conference consensus 2011, its BC approximations were applied to classify BC into five subtypes: estrogen receptor (ER) and/or progesterone receptor (PgR) positive, HER2 negative, and low Ki67 (<14%) [luminal A]; ER and/or PgR positive, HER2 negative and high Ki67(≥ 14%) [luminal B/HER2 negative]; ER and/or PgR positive, any Ki67 and HER2 positive [luminal B/HER2 positive]; ER negative, PgR negative and HER2 positive [HER2 positive/nonluminal]; and ER negative, PgR negative and HER2 negative [triple negative]. Cumulative incidences of LRR were compared across different subgroups by means of the Gray test. Multivariable Cox regression models were applied.nnnRESULTSnMedian follow up time was 74 months (range 3-165). The cumulative incidence of LRR was 5.5% (121 events). The 5-year cumulative incidence of LRR was 2.5% for luminal A; 5.0% for luminal B/HER2 negative; 9.8% for luminal B/HER2 positive; 3.8% for HER2 non luminal; and 10.9% for triple negative. On multivariable analysis, tumor size (pT) >2 cm, body mass index (BMI) ≥ 25, triple negative and luminal B/HER2 positive subtypes were associated with increased risk of LRR.nnnCONCLUSIONnLuminal B/HER2 positive, triple negative subtypes and BMI ≥ 25 are independent prognostic factors for risk of LRR after IBR.

Sarcoma of the Breast: Outcome and Reconstructive Options

INTRODUCTIONnSurgery is the mainstay of treatment for all breast sarcomas. The role of adjuvant chemotherapy and radiation therapy has not been clearly defined. The aim of this single-center retrospective study was to analyze prognostic factors, outcome, and recent advances.nnnMATERIALS AND METHODSnData from 203 patients with all breast sarcomas treated in a single center were collected from 1996 to 2010. Phyllodes tumors and metastatic disease at presentation were excluded from the population. Thirty-six women and 1 man were included in the analysis. Local recurrence, metastatic disease, survival, and reconstructive outcome were evaluated.nnnRESULTSnThirty-four patients out of 37 (91.9%) had an angiosarcoma and 3 had a stromal sarcoma (8.1%). Twenty-one patients (56.8%) had previously undergone breast radiation therapy for breast carcinoma or lymphoma. Twenty-six patients (70.3%) underwent mastectomy, 14 of whom (53.8%) with breast reconstruction. Thirty-six patients (97.3%) had free margins, 1 (2.7%) had a microscopically focally involved margin after surgery. Five patients received adjuvant chemotherapy and 6 received adjuvant radiation therapy. Median follow-up was 58 months (range, 4-146 months). Twelve sarcoma-related deaths were observed with a 5-year cumulative incidence of 43.4%. Twenty-four sarcoma-related events were observed with a 5-year cumulative incidence of 70.8%. The same figure was 49.7% in patients affected by primary sarcoma and 85.7% in patients with secondary sarcoma (P = .06).nnnCONCLUSIONnSecondary sarcomas were associated with a higher risk of events. Patients undergoing breast conservative surgery or reconstruction after mastectomy did not show a worse prognosis compared with patients undergoing mastectomy.

Mastectomy without radiotherapy : outcome analysis after 10 years of follow-up in a single institution

The aim of this study was to identify the prognostic factors associated with the risk of loco-regional recurrence (LRR) of women undergoing mastectomy and complete axillary dissection without radiotherapy. We analyzed data from 650 women operated between 1997 and 2001 in a single institution. Median follow-up was 10xa0years. Overall survival was 89.8 % at 5xa0years and 76.6 % at 10xa0years. The 10-year cumulative incidence of LRRs was 10.0 % (5.0, 10.5, 15.8, and 18.5 % in patients with 0, 1–3, 4–9, and ≥10 positive lymph nodes (LNs), respectively). Sixty-two (9.5 %) LRRs were observed, 5 (0.8 %) of which occurred in the axillary LNs. Supraclavicular LNs recurrences (nxa0=xa016, 2.5 %) occurred more frequently in patients with four or more positive LNs, Ki-67xa0≥xa020 % or extensive peritumoral vascular invasion (PVI). At multivariable analysis, nodal status was the only prognostic factor for local events, while nodal status, Ki-67 and PVI were significant prognostic factors for recurrences in the regional LNs. Moreover, within each category of positive LNs, high values of Ki-67 and extensive PVI were associated with the highest risk of LRR while low values of Ki-67 and absence of extensive PVI were associated with the lowest risk of LRR. Women with node-negative tumors have the lowest risk of LRR and represent the group of patients that might benefit the least from radiotherapy. PVI and Ki-67 might help tailoring PMRT indications among patients with positive LNs. Finally, the very low incidence of recurrences in the axillary LNs raises questions about the inclusion of the axilla in the radiation field.

Prognostic role of CA15.3 in 7942 patients with operable breast cancer

To assess the prognostic value of presurgical CA15.3 in a large cohort of patients with early breast cancer. A total of 7.942 consecutive patients with breast cancer operated at the European Institute of Oncology between 1998 and 2005 and with presurgical values of CA 15.3 available were included. We explored patterns of recurrence by baseline CA 15.3 values. Mean CA15.3 was 17.0xa0U/ml. CA15.3 was associated with age, tumor size, nodal involvement, Ki-67 labeling index, grade, HER2 expression, molecular subtype, and perivascular invasion. CA15.3 was independently associated with distant metastases [HRxa0>xa020xa0U/ml vs. ≤xa020xa0U/ml: 1.34 (95% CI 1.15–1.56)] and death [HRxa0>xa020xa0U/ml vs. ≤xa020xa0U/ml: 1.30 (95% CI 1.11–1.53)]. When considering CA15.3 as continuous variable, we observed a constant risk of metastasis and death from the lowest values to about 15–20xa0U/ml, and then a significantly increasing risk with increasing values of CA15.3. Finally, CA15.3 provided significant additional information to the common prognostic factors to predict the occurrence of metastases (C-index P value 0.04). In patients with operable breast cancer, presurgical CA15.3 value is an independent prognostic factor for metastases and deaths. CA15.3 provides additional information to the common prognostic factors and should be considered in the adjuvant therapeutic algorithm.

Locoregional recurrence in patients with HER2 positive breast cancer.

Literature shows that HER2/neu positive breast cancer cells are more sensitive to radiation-induced apoptosis by targeting the epidermal growth factor receptor family tyrosine kinase. We selected 466 patients with pT1-2 HER2/neu positive tumors who received adjuvant trastuzumab for primary invasive breast cancer. Patients were divided into three groups [Quadrantectomy followed by conventional radiotherapy vs Quadrantectomy followed by Intra-operative radiotherapy with electrons vs Mastectomy without radiotherapy]. After a median follow-up of 52 months, the 5-year cumulative incidence of locoregional recurrence (LRR) was 1.9%, 11.5% and 5.0% respectively (p < 0.01). At the multivariate analysis, extensive perivascular invasion, Luminal B HER2/Progesterone Receptor (PgR) negative status and Quadrantectomy followed by Intra-operative radiotherapy with electrons have significantly increased the risk of LRR. Our results suggest that HER2/neu positive breast cancer might have better outcomes when treated simultaneously with external radiotherapy and trastuzumab. Moreover, we underline the importance of PgR and further new stratification of risk among luminal subtypes.

Factors predicting worse prognosis in patients affected by pT3 N0 colon cancer: long-term results of a monocentric series of 137 radically resected patients in a 5-year period

Background and purposeFor patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial. The purpose of this study was to identify clinical and/or pathological findings related to a worse prognosis in this category of patients.Patients and methodsWe retrospectively analyzed the data of consecutive patients, extracted by an institutional Tumour Registry, admitted to an affiliated University Hospital in Milan (European Institute of Oncology) for adenocarcinoma of the colon (all sites), between 2000 and 2005, and having a final pT3 N0 pathology staging after curative surgery. Adjuvant chemotherapy was decided as a result of a medical decision within a multidisciplinary Tumor Board.ResultsData of 137 patients were obtained, with a median follow-up of 77xa0months (range 6–131). Patients who received chemotherapy were younger than patients who did not. Nine patients out of 137 (6.5xa0%) died as a consequence of colon cancer recurrence; four of them had received adjuvant chemotherapy. Only histological grade III and mucinous histotype were found to impact on cumulative incidence of colon-related events (p 0.03 and 0.02, respectively); no impact was found on cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.74 and 0.74, respectively). Number of analyzed LNs (lymph nodes) emerged as a factor possibly affecting the cumulative incidence of colon-related events (p 0.09) as well as the cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.10). The risk of events was inversely proportional to the number of dissected LNs, even over 20 up to about 25 LNs. Never-smokers exhibited a lower incidence of colon-related events, although the difference was not statistically significant (p 0.09). All other analyzed variables did not show any impact on survival rate, including age, gender, ASA score, BMI, site of colonic neoplasm, multifocality, perivascular invasion, and use of adjuvant chemotherapy.ConclusionsHistology grading G3 and mucinous histotype were predictors of worse outcome. Efforts to improve LN evaluation should result in clinically significant improvements in outcome, and also the quality of care for patients with radically resected stage II colon cancer.