Alberto Luini

IEO - Istituto Europeo di Oncologia, Milano, Lombardy, Italy

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Publications (322)1675.65 Total impact

  • Annals of surgery 10/2015; DOI:10.1097/SLA.0000000000001397 · 8.33 Impact Factor
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    ABSTRACT: No analyses have investigated the prognostic role of medial presentation in breast cancer patients on disease-free survival (DFS) and overall survival according to immunohistochemically-defined subtypes. We collected information from the institutional clinical database on consecutive breast cancer patients who underwent conservative surgery at the European Institute of Oncology, Milan, Italy, between 1994 and 2008. We compared the outcomes of patients with medial breast cancer with those of patients with nonmedial tumors observed at the institution during the same period. Among 7369 evaluable patients, 2254 (24%) had their primary tumors in medial quadrants and 7015 (76%) in other areas. Five-year DFS was 84.7% and 86.6% (P = .008) in patients with medial and nonmedial disease, respectively. In multivariate analysis, medial location was correlated with greater risk of recurrence (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.11-1.35; P < .0001) and death (HR, 1.27; 95% CI, 1.09-1.49; P = .0028). Medial presentation is an adverse prognostic factor for breast cancer patients. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Breast Cancer 07/2015; 15(6). DOI:10.1016/j.clbc.2015.07.003 · 2.11 Impact Factor

  • Cancer Research 05/2015; 75(9 Supplement):P1-15-05-P1-15-05. DOI:10.1158/1538-7445.SABCS14-P1-15-05 · 9.33 Impact Factor

  • Cancer Research 05/2015; 75(9 Supplement):P1-15-06-P1-15-06. DOI:10.1158/1538-7445.SABCS14-P1-15-06 · 9.33 Impact Factor
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    ABSTRACT: Background: Letrozole withdrawal for 3 months might permit estrogenic stimulation in residual resistant breast cancer disease susceptible to letrozole reintroduction. We investigated the impact of a 3-month letrozole-free interval on serum estradiol levels in patients with early stage breast cancer. Patients and methods: Postmenopausal women with estrogen receptor- and/or progesterone receptor-positive (> 10% of immunoreactive cells), node-negative early breast cancer were eligible. Patients received letrozole for 5 years with a 3-month treatment-free interval after the first year of therapy. The primary end point was to evaluate the increase in serum estradiol levels after a 3-month treatment-free interval. The secondary end points were the evaluations of other biologic markers (eg, follicle-stimulating hormone, luteinizing hormone, cholesterol, high-density lipoprotein, triglycerides, osteocalcin). Results: From November 2007 to February 2012, 130 evaluable patients were enrolled. The median age was 61 years. Mean values of estradiol levels at time of discontinuation were 5.6 pg/mL (standard deviation 1.7). Estradiol levels increased after a 3-month treatment-free interval by a mean of 3.3 pg/mL (66%; P < .0001). Follicle-stimulating hormone and luteinizing hormone levels decreased from baseline by a mean of 7.5 mU/mL (P < .0001), and 1.4 mU/mL (P = .0062), respectively. Triglycerides decreased from baseline by a mean of 8.6 mg/dL (P = .036), and osteocalcin increased by a mean of 2.8 ng/mL (P = .013). Conclusion: Intermittent letrozole significantly affects estradiol levels.
    Clinical Breast Cancer 04/2015; 15(5). DOI:10.1016/j.clbc.2015.03.007 · 2.11 Impact Factor
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    ABSTRACT: The aggressive biological behavior and the lack of target therapy prompts the search for new therapeutic approaches for triple-negative breast cancers. We evaluated the efficacy in terms of Ki-67 variation and clinical response but also the toxicity of a neoadjuvant regimen based on metronomic principles including ECF (epidoxorubicin with cisplatin on day 1 with low-dose 5-fluorouracil in continuous infusion every 21 days for 4 courses) followed by paclitaxel (90 mg/m(2)) on day 1, 8, and 15 every 28 days for 3 courses in combination with metronomic oral cyclophosphamide 50 mg/d for 12 weeks in patients with HER2-negative breast cancer (T2-T4a-d, N0-3, M0) with estrogen receptor and progesterone receptor < 10%. We enrolled 34 patients from June 2009 to May 2013. All were considered evaluable on an intention-to treat basis. The mean difference between the percentage of Ki-67 positive cells evaluated in surgical resection specimens and in pretreatment tumor core biopsy was 41% (95% confidence interval [CI], 30-51; P < .0001) for the entire population, and 22% (95% CI, 7-38; P = .0097) in patients who did not achieve pathological complete response (pCR). Responses to the treatment were obtained in 31 patients [91%] of the patients, and 19 patients (56%; 95% CI, 35-70) had a pCR. Stable disease was observed in 3 patients and none had progressive disease. Grade ≥ 3 hematologic adverse events included leukopenia in 9% (3 of 34), neutropenia in 38% (13 of 34), and anemia in 3% (1 of 34) of patients. Nonhematologic Grade ≥ 3 toxicities included only stomatitis in 1 patient. A neoadjuvant program with an ECF regimen followed by weekly paclitaxel with metronomic cyclophosphamide proved to be very effective, with high pCR rates, reduction of Ki-67, and it was associated with a low toxicity profile. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Breast Cancer 03/2015; 15(4). DOI:10.1016/j.clbc.2015.03.002 · 2.11 Impact Factor
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    ABSTRACT: To evaluate the tolerance of concomitant administration of anthracycline-based chemotherapy (CHT) and 3-dimensional conformal radiotherapy (RT) after breast-conserving surgery. Sixty-seven patients, treated with conservative surgery followed by 3-dimensional whole breast RT and concomitant CHT regimens including "Canadian modified" CEF (5-fluorouracil, epirubicin, cyclophosphamide) or AC (doxorubicin, cyclophosphamide) were evaluated for toxicity. They were compared in terms in compliance and acute toxicity with 67 patients irradiated sequentially after having received anthracyclines. Acute grade ≥2 skin toxicity was significantly higher in the concomitant group compared to the sequential group, although the incidence of Grade 3 desquamation showed no statistical difference (9% vs. 3%, p = 0.14). Haematological toxicity represented the main cause of treatment discontinuation, reporting higher rate of grade 3-4 leuco-neutropenia in the concomitant group (20.9% vs. 6%, p = 0.01). Mean RT duration was longer in the concomitant group (51 days vs. 45 days) owing to RT breaks. Late toxicity was acceptable. No symptomatic lung and heart events were reported. Radiological lung hyperdensity was detected in 27.7% of the patients in the concomitant group. Post-treatment left ventricular ejection fraction significantly decreased compared with baseline, but cardiac function remained within the normal range, without any difference between left or right-sided RT. Although there was more acute grade ≥2 skin toxicity in the concomitant group, the rate of grade 3 dermatitis was lower than expected, suggesting some advantages of 3-D CRT over older techniques. Haematological toxicity exerted a significant impact on both RT and CHT delivery.
    Tumori 02/2015; DOI:10.5301/je.5000218 · 1.27 Impact Factor
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    ABSTRACT: 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.
    Annals of Oncology 01/2015; 26(4). DOI:10.1093/annonc/mdv013 · 7.04 Impact Factor
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    ABSTRACT: The concept of a precise region in which to find the lymph nodes that drain the lymph directly from the primary tumor site can be traced back to a century ago to the observations of Jamieson and Dobson who described how cancer cells spread from cancer of the stomach in a single lymph node, which they called the “primary gland”. However, Cabanas was the first in 1977 to realize the importance of this concept in clinical studies following lymphography performed in patients with penile cancer. Thanks to Morton’s studies on melanoma in 1992, we began to understand the potential impact of the sentinel lymph node (SN) on the surgical treatment of this type of cancer. The use of a vital dye (blue dye) administered subdermally in the region surrounding the melanoma lesion led to the identification of the sentinel node, and the vital dye technique was subsequently applied to other types of solid tumors, e.g. breast, vulva. However, difficulties in using this technique in anatomical regions with deep lymphatic vessels, e.g. axilla, led to the development of lymphoscintigraphy, started by Alex and Krag in 1993 on melanoma and breast cancer and optimized by our group at European Institute of Oncology (IEO) in Milan in 1996. Today, lymphoscintigraphy is still considered as the most reliable method for the detection of the SN. In 1996, a new method for the localization of non-palpable breast lesion called radioguided occult lesion localization (ROLL) was also developed at IEO. Retrospective and prospective studies have since shown that the ROLL procedure permits the easy and accurate surgical removal of non-palpable breast lesions, overcoming the limitations of previous techniques such as the wire-guided localization. The purpose of this paper is to describe the evolution of SN biopsy and radioguided surgery in the management of breast cancer. We also include a review of the literature on the clinical scenarios in which SN biopsy in breast cancer is currently used, with particular reference to controversies and future prospects.
    01/2015; DOI:10.1007/s40336-015-0118-y
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    ABSTRACT: This retrospective study aimed to determine the feasibility, accuracy, and recurrence rates of lymphoscintigraphy and the new sentinel lymph node biopsy (SLNB) for patients with ipsilateral breast tumor recurrences who were treated previously with conservative surgery and had negative SLNB results. The study was conducted at the European Institute of Oncology in Milan and included 212 patients with the diagnosis of operable local breast cancer recurrence. They had been treated previously with conservative surgery and showed negative SLNB results. They subsequently underwent additional breast surgery and a second SLNB between May 2001 and December 2011. Preoperative lymphoscintigraphy demonstrated at least one new axillary sentinel lymph node (SLN) in 207 patients (97.7 %), whereas no drainage was observed in five patients (2.3 %). One or more SLNs were surgically removed from 196 of the 207 patients. Isolation of SLNs from the remaining 11 patients could not be accomplished. The success rate for the SLNB was 92.5 %. Extra-axillary drainage pathways were visualized in 17 patients (8 %). The annual axillary recurrence rate after a median follow-up period of 48 months was 0.8 %, and the cumulative incidence of axillary recurrence at 5 years was 3.9 %. A second SLNB should be considered for patients with operable local breast tumor recurrence who underwent conservative surgery and had negative SLNB results. The procedure is technically feasible and accurate for selected patients.
    Annals of Surgical Oncology 12/2014; 22(7). DOI:10.1245/s10434-014-4282-5 · 3.93 Impact Factor
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    ABSTRACT: Limited data are available on the prognostic value of changes in the biological features of residual tumours following neoadjuvant therapies in breast cancer patients. We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology (IEO), Milan, Italy, between 1999 and 2011. We selected patients who did not achieve pathological complete response (pCR) at final surgery. All patients had a pathological evaluation, including ER, PgR, HER2 protein and Ki-67 expression performed at the IEO both at diagnostic core biopsy and at final surgery. We identified a total of 904 patients. The 5% of patients who were ER-positive at diagnostic biopsy had ER-negative residual tumour at final surgery. For PgR expression, 67% of the patients, whose tumours had a PgR> 20% at diagnostic biopsy had a PgR<20% at final surgery. The Ki-67 expression changed from >20% to <20% in 40% of the patients. At the multivariate analysis the decrease of PgR -immunoreactive cells correlated with improved outcome in terms of DFS (HR 0.73; CI 0.54-1.00 p 0.046). In addition, the decrease of Ki-67 expression to<20% of the cells at final surgery was found to be associated with better outcome both in terms of DFS (HR 0.52; CI 0.40-0.68 p <0.0001) and OS (0.45 CI 0.32-0.64 p<0.0001) CONCLUSION: The decrease of PgR and Ki-67 expression after preoperative chemotherapy has a prognostic role in breast cancer patients with residual disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:
    Annals of Oncology 11/2014; 26(2). DOI:10.1093/annonc/mdu528 · 7.04 Impact Factor
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    ABSTRACT: Background Breast cancer occurs rarely in males accounting for approximately 1% of all breast carcinomas. Data on prognosis principally derives from retrospective studies and from extrapolation of female breast cancer series. Patients and methods A total of 99 male patients with invasive breast cancer were matched with 198 female breast cancer patients who had surgery at the same institution from 1999 to 2010. Matching variables were: year of surgery, age, primary tumor size, nodal involvement, hormone receptor status, status of HER2, ki67 and grade. Median follow-up was 8.6 years. Results Disease free survival (DFS) was significantly poorer in male breast cancer patients (10-year DFS 51.7% vs. 66.5%; HR 1.79; 95% CI 1.19-2.68; P=0.004). Similar results were observed for overall survival (OS) (10-year OS 70.7% vs. 84.2%; HR 1.79; 95% CI 1.01-3.15; P=0.043). The cumulative incidence (CI) of death for causes not related to the primary breast cancer was significantly higher for male rather than female breast cancer patients (HR 2.87, 95%CI 1.58-5.22;p= 0.001), while the breast cancer specific survival (BCSS) was similar between the two groups (10-year BCSS 81.5% vs. 88%; HR 1.27; 95% CI 0.62-2.59; P=0.517). Conclusions Our comparative series revealed that male breast cancer patients had a poorer DFS and OS when compared with female patients. Male patients showed also a higher risk of controlateral tumors and second primaries that contribute to the difference between the two groups. Appropriate counseling, surveillance, and prevention are recommended to improve survival for these individuals.
    Clinical Breast Cancer 10/2014; 14(5). DOI:10.1016/j.clbc.2014.02.008 · 2.11 Impact Factor
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    ABSTRACT: Aim It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance. Methods We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event. Results After a median follow-up of 7.0 years (interquartile range 5.4-8.9 years) survival for the series was high (91.3%; 95%CI 90.3-92.3 at 10 years) and only 91 (1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 ≥30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy. Conclusion Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival.
    European Journal of Surgical Oncology 10/2014; 40(10). DOI:10.1016/j.ejso.2014.07.041 · 3.01 Impact Factor
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    ABSTRACT: Treatment of diabetics with metformin is associated with decreased breast cancer risk in observational studies, but it remains unclear if this drug has clinical antineoplastic activity. In a recent presurgical trial, we found a heterogeneous effect of metformin on breast cancer proliferation (ki-67) depending upon insulin resistance (HOMA index). Here, we determined the associations of additional serum biomarkers of insulin resistance, tumor subtype, and drug concentration with ki-67 response to metformin. Two-hundred non-diabetic women were randomly allocated to metformin (850 mg/bid) or placebo for 4 weeks prior to breast cancer surgery. The ki-67 response to metformin was assessed comparing data obtained from baseline biopsy (ki-67 and tumor subtype) and serum markers (HOMA index, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, hs-CRP, adiponectin) with the same measurements at definitive surgery. For patients with a blood sample taken within 24 h from last drug intake, metformin level was measured. Compared with placebo, metformin significantly decreased ki-67 in women with HOMA > 2.8, those in the lowest IGFBP-1 quintile, those in the highest IGFBP-3 quartile, those with low free IGF-I, those in the top hs-CRP tertile, and those with HER2-positive tumors. In women with HOMA index > 2.8, drug levels were positively correlated with the ki-67 decrease, whereas no trend was noted in women with HOMA < 2.8 (p-interaction = 0.07). At conventional antidiabetic doses, the effect of metformin on tumor ki-67 of non-diabetic breast cancer patients varies with host and tumor characteristics. These findings are relevant to design breast cancer prevention and treatment trials with metformin. Electronic supplementary material The online version of this article (doi:10.1007/s10549-014-3141-1) contains supplementary material, which is available to authorized users.
    Breast Cancer Research and Treatment 09/2014; 148(1). DOI:10.1007/s10549-014-3141-1 · 3.94 Impact Factor
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    ABSTRACT: Introduction: Despite the great strides made in medical knowledge, surgery still remains a necessary part of the breast cancer treatment. Surgical procedures still lead to post surgical sequelae. The axillary web syndrome (AWS) is one such sequela, which can lead to disability, reduced arm mobility and compromised quality of life. It is often unidentified and the literature regarding its assessment is limited. To improve diagnosis and patient education, the Screening Test AWS (ST-AWS) questionnaire was drafted and applied at the European Institute of Oncology (EIO). Materials and method: We prospectively recruited patients from October 2012 to December 2012. Patients who underwent sentinel lymph node biopsy and/or axillary dissection procedures were registered. Physical examination was set as a gold standard. Results: 88 patients completed the questionnaire. Among these, 32 patients had axillary web syndrome diagnosed, thus a 36% incidence. The questionnaire achieved a sensitivity of 94%, a specificity of 91%, a positive prevalence value (PPV) of 86%, a negative prevalence value (NPV) of 96% and an accuracy of 92%. Conclusion: Our questionnaire achieves high sensitivity and predictive values, and we would recommend it as a screening-tool for auto-diagnosis of the AWS. The main objective of the questionnaire is to enhance patient and therapist awareness of the problem, and prompt management to shorten the effects of this disability. Moreover, it may offer a tool to enhance body image acceptance after surgery. Further studies whereby the efficacy of the questionnaire is investigated in a larger, heterogeneous group and in different situations are warranted.
    The Breast 09/2014; 23(6). DOI:10.1016/j.breast.2014.09.001 · 2.38 Impact Factor
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    ABSTRACT: Rational We retrospectively analyzed 232 patients affected by well differentiated ductal intraepithelial neoplasia (DIN1c or DCIS G1) treated with conservative surgery without adjuvant radiotherapy. Results 25 invasive and 18 non-invasive local recurrences were observed (median follow-up 80 months; 5-year cumulative incidence: 12.2%). Seven of the 15 young patients (<40 y) developed local recurrence (2 in situ, 5 invasive). Age <50 (HR 1.89, 95% C.I. 1.01–3.45), multifocality (HR 3.21, 95% C.I. 1.46–7.06), Ki-67 > 7% (HR 2.33, 95% C.I. 1.20–4.55) and surgical margins <10 mm (HR 2.00, 95% C.I. 1.06–3.76) were significantly associated with an increased risk of local recurrence. Conclusions Young age, multifocality and small margins appeared as clear risk factors of local recurrence in DIN1c (DCIS G1) population. The presence of multiple poor prognostic features warrant a thorough discussion regarding local treatment.
    The Breast 09/2014; 23(6). DOI:10.1016/j.breast.2014.08.016 · 2.38 Impact Factor
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    ABSTRACT: It is a well-established multidisciplinary practice at the European Institute of Oncology, that nurses and physicians often report their difficulties to clinical psychologists regarding adherence to hospital scheduling and procedures, when faced with women who, having been diagnosed with cancer, may be too overwhelmed to understand medical advice. We thus undertook an observational-prospective-cohort study, to investigate the prevalence and variation of PTSD symptomatology in women awaiting a mastectomy at a mean of 30 days after diagnosis and up to 2 years after discharge from hospital. The presence of any correlations between PTSD symptoms and medical and psycho-social variables was also investigated. Between March 2011 and June 2012, 150 women entered the study and were evaluated at four points in time: pre-hospital admission, admission for surgery, hospital discharge and two years later. The prevalence of distress at pre-hospital admission was 20% for intrusion symptoms, 19.1% for avoidance symptoms and 70.7% for state anxiety. Intrusion was negatively correlated with time from diagnosis independently of tumor dimensions, i.e. independently of the perceived seriousness of the illness. Even though at two-year follow up the prevalence of intrusion and avoidance is similar to that in the general population, patients with high levels of intrusion and avoidance at pre-hospital admission will maintain these levels, showing difficulties in adjusting to illness even two years later. As for psycho-social factors, the presence of a positive cancer family and relational history is associated with high levels of distress, in particular with intrusive thinking. Proper interventions aimed at the management of these issues and at their implications in clinical practice is clearly warranted.
    SpringerPlus 07/2014; 3(1):392. DOI:10.1186/2193-1801-3-392
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    ABSTRACT: Prognostic factors to better identify subcategories of node-positive breast cancer patients candidate to adjuvant chemotherapy are needed. The prognostic significance of the extent of peritumoral vascular invasion (PVI) in patients with positive axillary nodes is a matter of controversy. No data are available on the role of PVI within immunohistochemically defined subtypes. 3,729 consecutive patients with primary invasive breast cancer and positive axillary nodes were operated and referred for interdisciplinary evaluation from April 1997 to December 2005. Patients were classified as Luminal A, Luminal B(HER2 negative), Luminal B(HER2 positive), Triple Negative and HER-2 positive. The distribution of PVI was as follows: absent 2,010 (54 %), moderate/focal 963 (142 + 821) (26 %), and extensive 756 (20 %). Patients with extensive PVI were more likely to be Luminal B(HER2 negative) (49.3 %), younger (35-50 years), to have larger tumors (>pT2) with higher grade, a higher extent of node involvement (>4 nodes) and higher proliferative index, compared with patients with absence or moderate/focal PVI (p < 0.0001). In the multivariate analysis, extensive PVI (vs. absent) was correlated with a significant higher risk of local recurrence (HR 1.42, 95 %CI, 1.03-1.95, p = 0.0301). The immunohistochemically defined Luminal A-like subtype had a significant better outcome in terms of DFS, OS and reduced incidence of distant metastases when compared with the other subtypes. The occurrence of extensive PVI correlates with an increased risk of local recurrence. Luminal A tumors, classified according to the most recent St. Gallen recommendations, had an excellent outcome irrespective to the occurrence of extensive PVI or lymph node metastases and might be a good candidate to personalized adjuvant treatments.
    Breast Cancer Research and Treatment 07/2014; 146(3). DOI:10.1007/s10549-014-3043-2 · 3.94 Impact Factor
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    ABSTRACT: Introduction: The St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 recognized substantial progress in the pathological characterization of breast cancer subtypes. A useful surrogate definition was developed to distinguish luminal A-like breast cancer from luminal B-like disease based on a combination of estrogen receptor (ER), progesterone receptor (PgR) and Ki-67 status, without a requirement for molecular diagnostics. Differences depend upon the choice of the threshold value for Ki-67 and the requirement for substantial PgR positivity. We aimed to verify the suitability of the new surrogate definitions of luminal subtypes in terms of distant disease control in a large series of patients. Methods: We studied 9,415 women with a median follow-up of 8.1 years who (1) had ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer and (2) had undergone surgery at the European Institute of Oncology between 1994 and 2006. We evaluated distant disease-free survival of patients with "low" (<14%), "intermediate" (14% to 19%) or "high" (≥20%) Ki-67 positivity stratified by PgR expression (negative or low versus high). We calculated the cumulative incidence of distant events, considered competing events and performed multivariable analysis adjusted for pathologic tumor stage, pathologic node stage, tumor grade, peritumoral vascular invasion and menopausal status. Results: Lack of substantial PgR positivity was associated with poorer outcomes only for patients with an intermediate Ki-67 level (P<0.001). The 4,890 patients (51.9%) with low Ki-67 level (any PgR expression level) or with intermediate Ki-67 level but substantial PgR positivity had comparably good outcomes and thus may represent a most advantageous grouping of those with luminal A-like disease. Conclusions: The updated pathological definition of intrinsic molecular subtypes may maximize the number of patients classified as having the luminal A-like intrinsic subtype of breast cancer and for whom the use of cytotoxic drugs could mostly be avoided.
    Breast cancer research: BCR 06/2014; 16(3):R65. DOI:10.1186/bcr3679 · 5.49 Impact Factor

  • The Breast Journal 05/2014; 20(4). DOI:10.1111/tbj.12295 · 1.41 Impact Factor

Publication Stats

18k Citations
1,675.65 Total Impact Points


  • 1996-2015
    • IEO - Istituto Europeo di Oncologia
      • • Division of Breast Cancer Surgery
      • • Division of Pathology
      • • Division of Nuclear Medicine
      Milano, Lombardy, Italy
  • 2001-2012
    • University of Milan
      Milano, Lombardy, Italy
  • 1989-2012
    • CRO Centro di Riferimento Oncologico di Aviano
      • Division of Surgical Oncology
      Aviano, Friuli Venezia Giulia, Italy
  • 1995-2002
    • Memorial Sloan-Kettering Cancer Center
      • Department of Surgery
      New York City, NY, United States
  • 1977-1997
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 1987-1995
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy