Jacopo Nori

Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial

BACKGROUND Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC. METHODS This study was performed at the University of Florence (Florence, Italy). Women aged more than 40years affected by early BC, with a maximum pathological tumour size of 25mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the tumour bed of 10Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895. FINDINGS A total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4-7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1-3.0) and in the WBI group (three cases; 95% CI 0.0-2.8). No significant difference emerged between the two groups (log rank test p=0.86). We identified seven deaths in the WBI group and only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p=0.0001), late (p=0.004), and cosmetic outcome (p=0.045). INTERPRETATION To our knowledge, this is the first randomised study using the IMRT technique for APBI delivery. No significant difference in terms of IBTR and overall survival was observed between the two arms. APBI displayed a significantly better toxicity profile.

Radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy: Analysis of 49 cases from a single-centre and review of the literature

The purpose of this study was to evaluate the reliability of image-guided 14-gauge needle core biopsy in the diagnosis of radial scar without associated atypical epithelial proliferation, by comparison with definitive histological diagnosis on surgical excision. The records of 8792 consecutive image-guided 14-gauge needle core biopsy of the breast performed from January 1996 to December 2009 were reviewed. Forty-nine cases of radial scar without associated atypical epithelial proliferation were identified and compared with definitive histological diagnosis on surgical excision. The definitive histological diagnosis on surgical excision confirmed the results of image-guided 14-gauge needle core biopsy in 36 of 49 cases (73.5%), in 9 cases (18.3%) radial scar was associated with atypical epithelial proliferation, while 4 cases out of 49 cases were upgraded to carcinoma (3 cases of ductal carcinoma in situ and one case of invasive lobular carcinoma), with an underestimation rate of 8.2%. A diagnosis of radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy does not exclude a malignancy on surgical excision; consequently during the multidisciplinary discussion further assessment by surgical excision or vacuum-assisted excision, as recently reported, needs to be considered to obtain a definitive histological diagnosis.

Indications for breast magnetic resonance imaging. Consensus document “Attualità in senologia”, Florence 2007

The clinical use of breast magnetic resonance (MR) imaging is increasing, especially for applications requiring paramagnetic contrast-agent injection. This document presents a synthetic list of acceptable indications with potential advantages for women according to evidence from the literature and the expert opinion of the panel that developed this statement. We generally recommend that breast MR imaging be performed in centres with experience in conventional breast imaging [mammography and ultrasonography (US)] and needle-biopsy procedures (under stereotactic or US guidance) as well as in breast MR imaging and second-look US for findings not revealed by conventional imaging performed before MR imaging. In our opinion, there is no evidence in favour of breast MR imaging as a diagnostic tool to characterise equivocal findings at conventional imaging when needle-biopsy procedures can be performed, nor for the study of asymptomatic, non-high-risk women with negative conventional imaging. After a description of technical and methodological requirements, we define the indications and limitations of breast MR imaging for surveillance of high-risk women, local staging before surgery, evaluation of the effect of neoadjuvant chemotherapy, breast previously treated for carcinoma, carcinoma of unknown primary syndrome, nipple discharge and breast implants.RiassuntoLa RM mammaria è in fase di crescente utilizzo clinico, soprattutto per le applicazioni che richiedono la somministrazione di mezzo di contrasto (MdC) paramagnetico. Il presente documento propone una codificazione sintetica delle indicazioni accettabili con potenziale vantaggio per le donne, secondo la valutazione delle evidenze presenti in letteratura e l’opinione del gruppo di esperti estensori del documento. In generale si raccomanda che l’indagine sia eseguita presso centri che siano in grado di combinare l’esperienza senologica relativa all’imaging convenzionale e ai prelievi agobioptici con quella specifica in RM mammaria e che garantiscano l’esecuzione del second look ecografico per i reperti non rilevati all’imaging convenzionale pre-RM. Non si ritiene che vi siano evidenze in favore dell’utilizzo della RM quale approccio diagnostico nella caratterizzazione di reperti equivoci all’imaging convenzionale in tutte le situazioni nelle quali sia praticabile il prelievo agobioptico sotto guida ecografica o stereotassica né in favore dello studio di donne non ad alto rischio asintomatiche e con imaging convenzionale negativo. Sono qui definiti i requisiti tecnici e metodologici di esecuzione dell’indagine e indicazioni e limiti relativi a: sorveglianza delle donne ad alto rischio di tumore mammario; stadiazione locale pretrattamento chirurgico; valutazione dell’effetto della chemioterapia neoadiuvante; mammella trattata per carcinoma; carcinoma unknown primary syndrome; mammella secernente; protesi mammarie.

Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer.

The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node‐negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status.

Subcutaneous Direct-to-Implant Breast Reconstruction: Surgical, Functional, and Aesthetic Results after Long-Term Follow-Up

Background: Direct-to-implant breast reconstruction can be achieved more easily by means of soft-tissue replacement devices such as dermal matrices and synthetic meshes. The feasibility of a subcutaneous approach has been recently investigated by some studies with different devices functioning as implant support. Aim of this study is to analyze the long-term results, both objective and subjective, of a previous nonrandomized trial comparing prepectoral (subcutaneous) and retropectoral breast reconstructions. Methods: Patients enrolled in a nonrandomized prospective trial, comparing the standard retropectoral reconstruction and the prepectoral subcutaneous approach, using a titanium-coated mesh in both techniques, were followed up and evaluated for long-term results. Cases were compared in terms of the causes and rate of reinterventions, of the postoperative BREAST-Q questionnaire results, and of an objective surgical evaluation. Results: The subcutaneous group had a rate of implant failure and removal of 5.1% when compared with 0% in the retropectoral group. Aesthetic outcome was significantly better for the subcutaneous group both at a subjective and at an objective evaluation. Capsular contracture rate was 0% in the subcutaneous group. Conclusions: A higher rate of implant failure and removal, although not significant, always because of skin flaps and wound problems, should be taken into account for a careful patients selection. The subcutaneous breast reconstruction shows good long-term results. A coherent subjective and objective cosmetic advantage of this approach emerges. Moreover, no capsular contracture is evident, albeit in a relatively limited number of cases.

Preoperative assessment of HER-2/neu status in breast carcinoma: the role of quantitative real-time PCR on core-biopsy specimens.

OBJECTIVES Knowledge of HER-2/neu status is mandatory to identify breast cancer patients amenable to trastuzumab treatment. We evaluated the diagnostic performance of quantitative real-time polymerase chain reaction (qRT-PCR) in the preoperative determination of HER-2/neu status in breast cancer, using core biopsy material. METHODS In a prospective series, qRT-PCR was performed on fresh core biopsy specimens taken preoperatively in 87 patients with breast carcinoma. Cases with qRT-PCR ratio > or = 2.0 were considered to have HER-2/neu amplification. The results of RT-PCR analysis were compared with those of the standard immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) methods. Cases with IHC 3+ or with IHC 2+ and FISH showing amplification were considered HER-2/neu positive. All other cases were considered HER-2/neu negative. RESULTS qRT-PCR showed HER-2/neu amplification in 13 cases (14.9%), while the standard IHC-FISH combined approach identified 17 HER-2/neu-positive cases (19.5%). Overall, there was concordance between methods in 83 of 87 patients (95.4%). The Spearmans rho correlation coefficient was 0.851; p<0.001. The diagnostic performance for preoperative diagnosis of HER-2/neu status using RT-PCR on core biopsy specimens as compared to standard approach was as follows: sensitivity 76.5%; specificity 100%; positive predictive value 100%; negative predictive value 94.6%. CONCLUSIONS Quantitative RT-PCR determination of HER-2/neu status from core biopsy specimens provided results comparable to those given by the standard IHC and FISH methods. The use of qRT-PCR on core biopsy material may represent a very useful and easy tool to enhance early identification of HER-2/neu-positive breast cancer patients who, possibly can benefit from trastuzumab treatment.

Predicting the status of axillary lymph nodes in breast cancer: A multiparameter approach including axillary ultrasound scanning

In a prospective study, we attempted to predict axillary metastases in 135 breast cancer patients by a preoperative multiparameter evaluation including axillary ultrasound scanning (US). After surgery, factors associated with lymph node metastases by univariate analysis were included in a multivariate model. By multivariate analysis, the stronger independent predictors of lymph node metastases were suspicious axillary US (p<0.001), tumor location in the outer quadrants (p=0.001) and high Ki-67 index (>10%) (p=0.002). A predictive model based on these variables, identified a high-risk group (20.0%) represented by women with suspicious axillary US, tumor in the outer quadrants and high Ki-67 index, with axillary metastases in 100%, whereas all patients with opposite features (8.1%) had uninvolved axillary lymph nodes. This multiparameter evaluation including axillary US may be used to optimize the selection of breast cancer patients candidate to sentinel lymph node biopsy or axillary lymph node dissection. The accuracy of this predictive model still requires prospective validation in a larger sample of women.

Role of ultrasound and sonographically guided core biopsy in the diagnostic evaluation of ductal carcinoma in situ (DCIS) of the breast

PurposeThe aim of this study was to evaluate the role of ultrasound (US)-guided core biopsy in the diagnosis of ductal carcinoma in situ (DCIS) and to correlate the histological results on percutaneous biopsy and surgical excision.Materials and methodsOut of 2,423 consecutive core biopsies performed under US guidance, we evaluated 65 lesions with a histological diagnosis of DCIS. All patients underwent mammography, high-frequency broadband US and percutaneous breast biopsy with a 14-gauge needle and a mean number of five samples (range 4–7 passes). Surgical excision was performed in all cases, and the histological results on the surgical specimen were correlated with those on core biopsy samples. The sonographic features of DCIS lesions were described, comparing pure DCIS (those confirmed by definitive histology) and DCIS with invasive component at surgical excision.ResultsTwenty-seven out of 65 DCIS at core biopsy were found to have an invasive or microinvasive component at surgical excision, leading to rate of histological underestimation of core biopsy of 41.5%. The most frequent sonographic appearances were: (a) mass without microcalcifications (47.4% of pure DCIS, 63% of DCIS with invasive component); (b) mass with microcalcifications (23.7% of pure DCIS, 22% of DCIS with invasive component); (c) isolated microcalcifications (10.5% of pure DCIS); (d) ductal abnormalities (18.4% of pure DCIS, 15% of DCIS with invasive component).ConclusionsDue to the high underestimation rate of core biopsy, caution is mandatory in the case of DCIS diagnosis on core biopsy. Although some histological features (such as stromal fibrosis, periductal inflammatory infiltrate, high nuclear grade) can suggest the presence of an invasive component, the sonographic appearance of DCIS cannot be used to predict the cases that are underestimated on US-guided core biopsy. Nevertheless, a sonographically detectable solid component, either inside dilatated ducts or associated with microcalcifications, and a size greater than 20 mm are frequently associated with the presence of an invasive component.RiassuntoObiettiviValutare l’apporto della biopsia percutanea ecoguidata nella diagnosi del carcinoma duttale in situ, correlando i risultati della biopsia percutanea con l’esame istologico definitivo sul pezzo chirurgico.Materiali e metodiSu 2423 core biopsy consecutive sono state valutate 65 lesioni con diagnosi istologica percutanea di carcinoma duttale in situ (CDIS). Tutte le pazienti hanno eseguito l’esame mammografico e successivamente ecografico con sonda ad alta frequenza a larga banda, e la biopsia percutanea con aghi da 14 G con un numero medio di 5 frustoli (range 4–7). Tutte le pazienti sono state sottoposte a intervento chirurgico; la diagnosi istologica definitiva (sul pezzo operatorio) è stata confrontata con la diagnosi bioptica percutanea. Sono stati descritti gli aspetti ecografici dei CDIS confrontando i CDIS puri (confermati cioè al successivo esame istologico definitivo) e i CDIS con componente invasiva alla verifica istologica definitiva dopo l’escissione chirurgica.RisultatiVentisette/65 lesioni con diagnosi bioptica percutanea di CDIS sono risultate associate a una componente infiltrante o microinfiltrante all’esame istologico definitivo, ottenendo pertanto una “sottostima istologica” della core-biopsy pari al 41,5%. Gli aspetti ecografici principali riscontrati più frequentemente sono stati: (a) massa senza microcalcificazioni (47,4% dei CDIS puri, 63% dei CDIS con componente invasiva); (b) massa con microcalcificazioni (23,7% dei CDIS puri, 22% dei CDIS con componente invasiva); (c) microcalcificazioni isolate (10,5% dei CDIS puri); (d) alterazioni duttali (18,4% dei CDIS puri, 15% dei CDIS con componente invasiva).ConclusioniL’elevata incidenza di sottostime istologiche alla core-biopsy impone un atteggiamento oltremodo prudente di fronte a una diagnosi di CDIS effettuata con la core-biopsy stessa. Sebbene alcune caratteristiche istologiche presenti nei frustoli bioptici prelevati (quali la fibrosi stromale, l’infiltrato infiammatorio periduttale, l’alto grado nucleare) possano suggerire la presenza di una componente invasiva, le caratteristiche ecografiche dei CDIS non possono essere utilizzate per predire i casi che vengono sottostimati alla biopsia percutanea eco-guidata. Tuttavia la presenza di una componente solida visibile ecograficamente, all’interno di immagini duttali o associata a calcificazioni, e le dimensioni superiori ai 20 mm possono talvolta far sospettare la presenza di una componente invasiva.

Breast Cancer in the Elderly: Treatment of 1500 Patients

Abstract:  There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This studys goal was to evaluate disease‐specific survival and local‐regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1–87.3 years).The median follow‐up was 8.7 years (range 1–30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan–Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease‐specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease‐free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors. 

Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 Patients treated with a prospective margin-directed policy

PURPOSE To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS). METHODS AND MATERIALS A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive. RESULTS After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence. CONCLUSIONS Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype.