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1.
Ann Surg Oncol ; 30(10): 6201-6214, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37606837

RESUMEN

BACKGROUND: Breast-conserving surgery (BCS) still remains a blind surgery despite all available tumor localization methods. Intraoperative ultrasound (IOUS) allows real-time visualization during all resection phases. METHODS: This was a prospective observational cohort study conducted at the Veneto Institute of Oncology between January 2021 and June 2022. Patients with ductal carcinoma in situ, T1-2 invasive cancer, or post-neoadjuvant tumors, suitable for BCS, were recruited. All breast cancer lesion types were included, i.e. solid palpable, solid non-palpable, non-solid non-palpable, and post-neoadjuvant treatment residual lesions. Eligible participants were randomly assigned to either IOUS or traditional surgery (TS) in a 1:1 ratio. The main outcomes were surgical margin involvement, reoperation rate, closest margin width, main specimen and cavity shaving margin volumes, excess healthy tissue removal, and calculated resection ratio (CRR). RESULTS: Overall, 160 patients were enrolled: 80 patients were allocated to the TS group and 80 to the IOUS group. IOUS significantly reduced specimen volumes (16.8 cm3 [10.5-28.9] vs. 24.3 cm3 [15.0-41.3]; p = 0.015), with wider closest resection margin width (2.0 mm [1.0-4.0] vs. 1.0 mm [0.5-2.0] after TS; p < 0.001). Tumor volume to specimen volume ratio was significantly higher after IOUS (4.7% [2.5-9.1] vs. 2.9% [0.8-5.2]; p < 0.001). IOUS yielded significantly better CRR (84.5% [46-120.8] vs. 114% [81.8-193.2] after TS; p < 0.001), lower involved margin rate (2.5 vs. 15%; p = 0.009) and reduced re-excision rate (2.5 vs. 12.5%; p = 0.032). CONCLUSIONS: IOUS allows real-time resection margin visualization and continuous control during BCS. It showed clear superiority over TS in both oncological and surgical outcomes for all breast cancer lesion types. These results disfavor the paradigm of blind breast surgery.


Asunto(s)
Neoplasias de la Mama , Procedimientos Quirúrgicos Ultrasónicos , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Márgenes de Escisión , Estudios Prospectivos , Ultrasonografía Intervencional
3.
Animals (Basel) ; 13(5)2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36899736

RESUMEN

Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties. EMT has been closely associated with cancer cell aggressiveness. The aim of this study was to evaluate the mRNA and protein expression of EMT-associated markers in mammary tumors of humans (HBC), dogs (CMT), and cats (FMT). Real-time qPCR for SNAIL, TWIST, and ZEB, and immunohistochemistry for E-cadherin, vimentin, CD44, estrogen receptor (ER), progesterone receptor (PR), ERBB2, Ki-67, cytokeratin (CK) 8/18, CK5/6, and CK14 were performed. Overall, SNAIL, TWIST, and ZEB mRNA was lower in tumors than in healthy tissues. Vimentin was higher in triple-negative HBC (TNBC) and FMTs than in ER+ HBC and CMTs (p < 0.001). Membranous E-cadherin was higher in ER+ than in TNBCs (p < 0.001), whereas cytoplasmic E-cadherin was higher in TNBCs when compared with ER+ HBC (p < 0.001). A negative correlation between membranous and cytoplasmic E-cadherin was found in all three species. Ki-67 was higher in FMTs than in CMTs (p < 0.001), whereas CD44 was higher in CMTs than in FMTs (p < 0.001). These results confirmed a potential role of some markers as indicators of EMT, and suggested similarities between ER+ HBC and CMTs, and between TNBC and FMTs.

4.
Br J Cancer ; 128(2): 266-274, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36396818

RESUMEN

BACKGROUND: The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. METHODS: Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. RESULTS: In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade ≥3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). CONCLUSIONS: We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Carboplatino/efectos adversos , Neoplasias de la Mama Triple Negativas/metabolismo , Paclitaxel/efectos adversos , Terapia Neoadyuvante , Antraciclinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfocitos Infiltrantes de Tumor/metabolismo
6.
J Clin Med ; 11(24)2022 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-36556118

RESUMEN

The main goal of our study was to evaluate the surgical technique, the feasibility and patient's satisfaction of multiple surgeries: Risk-reducing salpingo-oophorectomy (RRSO) combined with mastectomy in patients with BRCA 1-2 mutation carriers. We conducted a retrospective analysis of patients with BRCA 1-2 variants who underwent RRSO combined with risk-reducing bilateral mastectomy (RRBM) or surgeries for breast cancer from January-2015 to December-2021. We collected data about surgeries, complications, and patients' satisfaction using a questionnaire submitted 30 days after surgery. We included 54 patients. Forty-eight patients underwent RRSO, and six patients underwent RRSO + Total laparoscopic hysterectomy (LTH). The minor postoperative complications within 30 days were four: one breast seromas aspiration (1.9%), one infectious reconstructive complication treated with antibiotics therapy (1.9%), one Red-Breast-Syndrome (1.9%) and one trocar abdominal hematoma (1.9%) associated with RRSO. The major postoperative complications within 30 days were five: two evacuations of a breast hematoma (3.7%) and three infectious reconstructive complications treated with removal expander/implant (5.6%). No postoperative complications after 30 days were observed. According to the satisfaction questionnaire, more than 90% of patients were satisfied and would have combined surgery again. In conclusion, the multiple surgeries seem feasible and safety with a single anesthesia, a single surgical time, a single postoperative recovery, and a high patients' satisfactions without increasing morbidity.

7.
NPJ Breast Cancer ; 7(1): 101, 2021 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-34341356

RESUMEN

Although 1% is the recommended cut-off to define estrogen receptor (ER) positivity, a 10% cut-off is often used in clinical practice for therapeutic purposes. We here evaluate clinical outcomes according to ER levels in a monoinstitutional cohort of non-metastatic triple-negative breast cancer (BC) patients undergoing (neo)adjuvant chemotherapy. Clinicopathological data of 406 patients with ER < 10% HER2-negative BC treated with (neo)adjuvant chemotherapy between 01/2000 and 04/2019 were collected. Patients were categorized in ER-negative (ER < 1%; N = 364) and ER-low positive (1-9%, N = 42). At a median follow-up of 54 months, 88 patients had relapsed and 64 died. No significant difference was observed in invasive relapse-free survival (iRFS) and overall survival (OS) according to ER expression levels, both at univariate and multivariate analysis (5-years iRFS 74.0% versus 73.1% for ER-negative and ER-low positive BC, respectively, p = 0.6; 5-years OS 82.3% versus 76.7% for ER-negative and ER-low positive BC, respectively, p = 0.8). Among the 165 patients that received neoadjuvant chemotherapy, pathological complete response rate was similar in the two cohorts (38% in ER-negative, 44% in ER-low positive, p = 0.498). In conclusion, primary BC with ER1-9% shows similar clinical behavior to ER 1% BC. Our results suggest the use of a 10% cut-off, rather than <1%, to define triple-negative BC.

8.
Breast ; 58: 93-105, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33991806

RESUMEN

Pre-operative localization of non-palpable breast lesions with non-wired non-ionizing (NWNI) techniques may improve clinical outcomes as reoperation rate, cosmetic outcome and contribute to organizational aspects improvement in breast-conserving surgery (BCS). However only limited literature is available and clinical studies involving these forefront devices are often small and non-randomized. Furthermore, there is a lack of consensus on free margins and cosmetic outcomes definitions. The objective of the present meta-analysis was to determine the crude clinical outcomes reported for the NWNI techniques on BCS. A literature search was performed of PubMed, Embase and Scopus databases up to February 2021 in order to select all prospective or retrospective clinical trials on pre-operative breast lesion localization done with NWNI devices. All studies were assessed following the PRISMA recommendations. Continuous outcomes were described in averages corrected for sample size, while binomial outcomes were described using the weighted average proportion. Twenty-seven studies with a total of 2103 procedures were identified. The technique is consolidated, showing for both reflectors' positioning and localization nearly the 100% rate of success. The re-excision and clear margins rates were 14% (95% CI, 11-17%) and 87% (80-92%), respectively. Overall, positive margins rates were 12% (8-17%). In studies that compared NWNI and wire localization techniques, positive margin rate is lower for the first techniques (12%, 6-22% vs 17%, 12-23%) and re-excision rate is slightly higher using the latter (13%, 9-19% vs 16%, 13-18%). Pre-operative NWNI techniques are effective in the localization of non-palpable breast lesions and are promising in obtaining clear (or negative) margins minimizing the need for re-excision and improving the cosmetic outcomes. Randomized trials are needed to confirm these findings.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Femenino , Humanos , Márgenes de Escisión , Mastectomía Segmentaria , Estudios Prospectivos , Reoperación , Estudios Retrospectivos
10.
ESMO Open ; 5(5): e000843, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33020219

RESUMEN

BACKGROUND: Phyllodes tumours (PTs) are rare fibroepithelial tumours accounting for <1% of all breast tumours. We assessed clinicopathological features and their prognostic effect in a single-institution patients' cohort. METHODS: Patients diagnosed with PT between 2001 and 2018 at our institution were identified. Clinical, surgical and pathological features were collected. Phyllodes-related relapse was defined as locoregional or distant recurrence (contralateral excluded), whichever first. RESULTS: A total of 166 patients were included: 115 with benign, 30 with borderline and 21 with malignant PTs. Features associated with malignant PT were younger age, larger T size, higher mitotic count, marked cytological atypia, stromal overgrowth, stromal hypercellularity, necrosis and heterologous differentiation (all p<0.01). The majority of patients with malignant PT underwent mastectomy (63.2% vs 3% of benign/borderline, p<0.001) and had negative surgical margins (83.3%). 4-year cumulative phyllodes-related relapse incidence was 7% for benign/borderline PT and 21.3% for malignant PT (p=0.107). In the entire cohort, marked cellular atypia and heterologous differentiation were associated with worse phyllodes-related relapse-free survival (HR 14.10, p=0.036 for marked vs mild atypia; HR 4.21, p=0.031 for heterologous differentiation present vs absent). For patients with benign PT, larger tumour size was associated with worse phyllodes-related relapse-free survival (HR 9.67, p=0.013 for T>5 cm vs T≤2 cm). Higher tumour-infiltrating lymphocytes (TILs) were associated with borderline and malignant PT (p=0.023); TILs were not associated with phyllodes-related relapse-free survival (HR 0.58, p=0.361 for TILs>2% vs≤2%). Overall, four patients died because of PT: three patients with malignant and one with borderline PT. CONCLUSIONS: Patients with malignant PT had increased rates of phyllodes-related relapse and phyllodes-related death. Cellular atypia and heterologous differentiation were poor prognostic factors in the entire cohort; large tumour size was associated with an increased risk of phyllodes-related relapse in benign PT.


Asunto(s)
Neoplasias de la Mama , Tumor Filoide , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Femenino , Humanos , Mastectomía , Recurrencia Local de Neoplasia/cirugía , Tumor Filoide/diagnóstico , Tumor Filoide/cirugía , Pronóstico , Estudios Retrospectivos
11.
Vet Pathol ; 57(6): 774-790, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32807036

RESUMEN

Mammary cancer is a common neoplasm in women, dogs, and cats that still represents a therapeutic challenge. Wnt/ß-catenin and Hippo pathways are involved in tumor progression, cell differentiation, and metastasis. The aim of this study was to evaluate mRNA and protein expression of molecules involved in these pathways in human (HBC), canine (CMT), and feline mammary tumors (FMT). Real-time quantitative polymerase chain reaction (qPCR) for ß-catenin, CCND1, YAP, TAZ, CTGF, and ANKRD1, western blotting for YAP, TAZ, and ß-catenin, and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), ERBB2, ß-catenin, and YAP/TAZ were performed on mammary tumor tissues. The protein expression of active ß-catenin was higher in tumors than in healthy tissues in all 3 species. The mRNA expression of the downstream gene CCND1 was increased in HBC ER+ and CMTs compared to healthy tissues. Membranous and cytoplasmic protein expression of ß-catenin were strongly negatively correlated in all 3 species. Tumors showed an increased protein expression of YAP/TAZ when compared to healthy tissues. Notably, YAP/TAZ expression was higher in triple negative breast cancers when compared to HBC ER+ and in FMTs when compared to CMTs. The mRNA expression of ß-catenin, YAP, TAZ, CTGF, and ANKRD1 was not different between tumors and healthy mammary gland in the 3 species. This study demonstrates deregulation of Wnt/ß-catenin and Hippo pathways in mammary tumors, which was more evident at the protein rather than the mRNA level. Wnt/ß-catenin and Hippo pathways seem to be involved in mammary carcinogenesis and therefore represent interesting therapeutic targets that should be further investigated.


Asunto(s)
Neoplasias de la Mama , Enfermedades de los Gatos , Enfermedades de los Perros , Neoplasias Mamarias Animales , Animales , Neoplasias de la Mama/veterinaria , Gatos , Transformación Celular Neoplásica , Perros , Femenino , Vía de Señalización Hippo , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , beta Catenina
12.
Oncologist ; 25(9): e1355-e1362, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32618068

RESUMEN

BACKGROUND: The integration of residual cancer burden (RCB) and post-treatment Ki67 as residual proliferative cancer burden (RPCB) has been proposed as a stronger predictor of long-term outcome in unselected patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT), as compared with RCB. However, no specific analysis in hormone-receptor-positive (HR+) human epidermal growth receptor 2-negative (HER2-) BC is available so far. MATERIALS AND METHODS: A cohort of 130 patients with HR+/HER2- BC who underwent NACT between 2000 and 2014 was included. Archival surgical specimens were evaluated for RCB. RPCB was calculated by combining RCB and Ki67 as previously described. Patients were categorized in four RCB and RPCB categories (pathological complete response and tertiles). Disease-free survival (DFS) and overall survival (OS) estimates were determined by Kaplan-Meier analysis and compared using the log-rank test. Overall change of χ2 and c-indexes were used to compare the performance of the prognostic models. RESULTS: RPCB was calculated for 85 patients. After a median follow up of 8.5 years, RCB was associated with OS (p = .048) but not with DFS (p = .152); RPCB was instead significantly associated with both DFS and OS (p = .034 and p < .001, respectively). In terms of OS, RPCB provided a significant amount of prognostic information beyond RCB (∆χ2 5.73, p < .001). In addition, c-index for OS prediction was significantly higher for RPCB as compared with RCB (0.79 vs. 0.61, p = .03). CONCLUSION: This is the first study evaluating RPCB in patients with HR+/HER2- BC treated with NACT. In this independent cohort, RPCB was a strong predictor of DFS and OS. The better performance of RPCB versus RCB was in part due to the ability of RPCB to discriminate a subgroup of patients with a particularly worse prognosis after NACT, who may be candidates for clinical trials evaluating novel adjuvant strategies. IMPLICATIONS FOR PRACTICE: The present work validated residual proliferative cancer burden (RPCB) as a strong predictor of long-term outcome in patients with hormone receptor-positive human epidermal growth receptor 2-negative (HR+/HER2-) breast cancer (BC) treated with neoadjuvant chemotherapy. In addition, results from the present study suggest RPCB as a promising tool to identify patients with HR+/HER2- BC who might potentially benefit from the inclusion in clinical trials evaluating novel or escalated postneoadjuvant treatment strategies because it allowed to discriminate a subgroup of patients with particularly poor prognosis despite having received subsequent endocrine therapy in the adjuvant setting.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Femenino , Hormonas , Humanos , Terapia Neoadyuvante , Neoplasia Residual/tratamiento farmacológico , Pronóstico , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico
14.
Oncologist ; 24(11): 1424-1431, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31152079

RESUMEN

BACKGROUND: The ROXANE Italian prospective study evaluated the impact of the 21-gene Recurrence Score (RS) results on adjuvant treatment decision for patients with early breast cancer. MATERIALS AND METHODS: Nine centers participated. Physicians used the RS test whenever unsure about adjuvant treatment recommendation for patients with estrogen receptor-positive/human epidermal growth receptor 2-negative, T1-T3, N0-N1 early breast cancer. Pre-RS and post-RS treatment recommendations were collected. RESULTS: A total of 251 patients were included. N0 patients (61%) showed higher grade (p < .001) and higher Ki67 (p = .001) and were more frequently progesterone receptor negative (p = .012) as compared with N1 patients. RS results were as follows: <11, n = 63 (25.1%); 11-25, n = 143 (57%); and ≥26, n = 45 (17.9%). Higher RS was found in N0 vs. N1 patients (p = .001) and in cases of G3 (p < .001) and higher Ki67 (p < .001). The rate of change in treatment decision was 30% (n = 75), mostly from chemotherapy (CT) plus hormone therapy (CT + HT) to hormone therapy (HT; 76%, n = 57/75). The proportion of patients recommended to CT + HT was significantly reduced from pre-RS to post-RS (52% to 36%, p < .0001). CT use reduction was more evident for N1 patients (55% to 27%) than for N0 patients (50% to 42%) and was observed only in cases of RS ≤17. CONCLUSION: Physicians predominantly used the 21-gene assay in N0 patients with a more aggressive biology or in N1 patients showing more indolent biology. In this selected patient population, the use of RS testing led to a 30% rate of change in treatment decision. In the N1 patient subgroup, the use of RS testing contributed to reduce CT use by more than half. IMPLICATIONS FOR PRACTICE: This study shows that, even in a context in which physicians recommend a high proportion of patients to endocrine treatment alone before knowing the results of the Recurrence Score (RS) assay, the use of the RS test, whenever uncertainty regarding adjuvant treatment recommendation is present, significantly contributes in further reducing the use of chemotherapy, especially for N1 patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias de la Mama/tratamiento farmacológico , Toma de Decisiones Clínicas , Perfilación de la Expresión Génica , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Bioensayo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/genética , Carcinoma Lobular/patología , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Italia , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Receptores de Progesterona/metabolismo , Tasa de Supervivencia
15.
Front Oncol ; 8: 581, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30560092

RESUMEN

Breast Cancer (BC) skin metastases represent a challenging clinical scenario. Although they usually arise when other distant metastases are already present, they may also represent a form of locoregional recurrence (LRR). Systemic therapy in this setting may have a role both in case a radical locoregional approach is unfeasible in order to achieve disease control, and as adjuvant strategy after radical removal of cutaneous lesions, in order to prevent or delay subsequent disease spread. Systemic therapy for HER2+ metastatic BC (MBC) currently relies on anti-HER2 targeted agents. In this context TDM1 is an option in trastuzumab-resistant patients.Here we present 2 cases of isolated skin metastases in patients with HER2+ BC progressing during or early after trastuzumab-based therapy, showing impressive responses to TDM1. We hypothesize that the unique properties of skin immune microenvironment may explain the failure of trastuzumab, which exerts its action also through immunological mechanisms, and the subsequent outlier responses to TDM1, that relies on a partially different mechanism of action.

16.
Oncologist ; 23(3): 297-305, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29133514

RESUMEN

BACKGROUND: The Breast DX Italy prospective study evaluated the impact of the 21-gene recurrence score (RS) result on adjuvant treatment decisions for patients with early breast cancer. MATERIALS AND METHODS: Nine centers (two Hub and seven Spoke centers of the Veneto Oncology Network) participated. Consecutive patients with estrogen receptor positive, human epidermal growth receptor negative, T1-T3, N0-N1 early breast cancer were prospectively registered; only those meeting protocol-defined clinicopathological "intermediate risk" criteria were eligible for the RS test. Pre-RS and post-RS physicians' treatment recommendations and treatment actually received were collected. RESULTS: A total of n = 124 N0 and n = 126 N1 patients underwent the RS assay. The majority had Grade 2 tumors (71%); median age was 55 years, median tumor size was 16 mm, and median Ki67 expression was 20%. Patients enrolled at Hub centers presented higher-risk features. The distribution of RS results was <18 (60.8%), 18-30 (32.4%), and >30 (6.8%). The indication before RS was hormonal therapy (HT) alone in 52% of cases. An indication before RS of chemotherapy (CT)+HT was more frequent for patients with N1 versus N0 tumors (57% vs. 39%, p = .0035) and for patients enrolled at Hub versus Spoke centers (54% vs. 36%, p = .007).The overall rate of change in treatment decision was 16% (n = 40), mostly from CT+HT to HT (n = 30). According to nodal status, rate of change in treatment decision was 12% for the N0 cohort and 20% for the N1 cohort. The proportion of patients recommended to CT+HT was significantly reduced from before to after RS (48% to 40%, p < .0016), especially in the N1 cohort (57% to 45%, p = .0027) and at Hub centers (54% to 44%, p = .001). CONCLUSION: Despite frequent indication of HT before RS, the use of the RS assay further contributed to sparing CT, especially for patients with N1 tumors and at Hub centers. IMPLICATIONS FOR PRACTICE: This study shows that, although a high proportion of patients were recommended to receive endocrine treatment alone before knowing the recurrence score (RS) assay, the RS test further contributed in sparing chemotherapy for some of these patients, especially in case of the N1 stage or for patients enrolled at referral centers. These data highlight the need for further work in collaboration with health authorities and companies in order to define strategies for the implementation of the use of RS testing in clinical practice in the Italian setting.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Toma de Decisiones Clínicas/métodos , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Perfilación de la Expresión Génica , Humanos , Italia , Metástasis Linfática/patología , Persona de Mediana Edad , Metástasis de la Neoplasia/genética , Recurrencia Local de Neoplasia/genética , Estudios Prospectivos , Receptores de Estrógenos/metabolismo
17.
Nucl Med Commun ; 38(6): 537-545, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28410290

RESUMEN

PURPOSE: The aim of this study was to assess the diagnostic and prognostic value of fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in patients with breast cancer (BC) in the preoperative and the postoperative setting. PATIENTS AND METHODS: Between 2011 and 2015, we prospectively enrolled 275 patients (mean age: 53 years) with BC (stage I-III; triple-negative or HER2-positive cancer). One-hundred and forty-nine (54.2%) patients underwent F-FDG PET/CT before neoadjuvant therapy and 126 (45.8%) after surgery and before any additional adjuvant therapy. The patients were followed for a median period of 44 (2-57) months. The different effects of PET/CT on the presetting and postsetting phase form a therapeutic and prognostic point of view were assessed by χ, by Kaplan-Meier, and Cox-regression analyses. RESULTS: In the preoperative setting, PET/CT provided additional diagnostic information in 42/149 (28%) patients. In particular, 17/70 (24%) patients at stage III were converted into stage IV and 4/68 (6%) at stage II were upstaged to IV. In the postoperative setting, PET/CT upstaged the disease in both stage IIIC and stage IV in 14/126 (11%) cases. At the end of follow-up, 28/271 (10%) patients died from BC and 40 (15%) had a recurrence of disease. On Kaplan-Meier analysis, patients with a positive PET/CT other than the primary tumor site showed both a worse overall survival and a worse disease-free survival compared with their counterpart (76 vs. 92%; P=0.063 and 65 vs. 100%; P<0.001). Conversely, in the postoperative setting, no differences in overall survival and disease-free survival were found between patients with positive and negative PET/CT findings (both P>0.05). On multivariate Cox-regression analysis, a positive PET/CT was a significant predictive factor of a poor prognosis in the preoperative setting. The significance was lost in the postoperative setting. CONCLUSION: In the preoperative setting, PET/CT can provide additional diagnostic and prognostic information. Conversely, in the postoperative setting, PET/CT adds diagnostic information, but does not provide any adjunctive prognostic assessment.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Periodo Preoperatorio , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Periodo Posoperatorio
18.
Q J Nucl Med Mol Imaging ; 61(2): 205-215, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25501326

RESUMEN

BACKGROUND: The primary endpoint of the study was to established the role of sestamibi scintimammography and PET/CT findings in locally advanced breast cancer (LABC) before neoadjuvant systemic therapy (NST) in different histological subtypes. The secondary endpoint was to determine the role of FDG PET/CT as multi-drug resistance marker. METHODS: From January 2012, we prospectively enrolled 51 consecutive women (median age: 49 years; range: 27-76 yrs) with a biopsy-proven LABC. All patients underwent both sestamibi scintimammography and FDG PET/CT within one week before to start NST. Both examinations were qualitatively and semiquantitatively analysed. For scintimammography we calculated the tumor to background ratio (T/B) and the most intense uptake of the tumor to background ratio (I/B) according the following formula: T/B=[cntsT-cntsB]/ [cntsB] and I/B [cntsI-cntsB]/[cntsB]. Furthermore, the percentage washout index (WO) for T and I were obtained, according to: WOT,I= [cntsT,I]early image-[cntsT,I]delayed image/[cntsT,I]early image. Maximum and average (avg) standardized uptake value (SUV) was computed by PET/CT, using a region of interest. Patients who had an evidence of systemic metastases or a second active cancer at imaging scans, were excluded. At the end of pre-operative therapy, the response to therapy was assessed by the analysis of surgical specimen and then correlated with both scintimammographic and PET/CT data. RESULTS: Based on the inclusion criteria, the final analysis was performed in 49 patients. Scintimammography and PET/CT showed a sensitivity of 100% for the evaluation of primary cancer, while PET/CT showed a slightly higher detection rate for axillary lymph node than scintimammography. According to the biological pattern, SUVmax and SUVavg resulted significantly different among histological subtypes, whereas scintimammographic data did not. At the end of neo-adjuvant therapy, pathological complete response was obtained in 12 (24.4%) patients, while 37 had a partial or no response to NST (identified as no-responders). On the basis of histopathological response to NST, median WOI resulted significantly lower in responders than non-responders (30.5% vs. 44%; P=0.027). Conversely, SUVmax and SUVavg were significantly higher in responders than non-responders (all P<0.05). In this latter subset of patients, high WOTs were associated with low SUVs. On the contrary, in responder group, high SUVs were reported particularly for high WOT values. CONCLUSIONS: Scintimammography with sestamibi did not accurately determine the responsiveness to therapy. FDG PET/CT is more accurate in the prediction of response to therapy, particularly in the aggressive LABC subtype. Moreover, semiquantitative data by FDG PET seems to be linked with the chemosensitivity to NST.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia , Mamografía , Terapia Neoadyuvante , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Femenino , Fluorodesoxiglucosa F18 , Humanos , Mamografía/métodos , Persona de Mediana Edad , Imagen Multimodal/métodos , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Estudios Prospectivos , Radiofármacos , Sensibilidad y Especificidad , Tecnecio Tc 99m Sestamibi , Resultado del Tratamiento , Imagen de Cuerpo Entero/métodos
19.
Eur J Nucl Med Mol Imaging ; 42(11): 1648-1655, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26025244

RESUMEN

PURPOSE: We investigated whether maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and whole-body (WB) SUVmax, WB MTV and WB TLG measured by (18)F-FDG PET/CT could improve prognostic stratification in patients with stage II/III breast cancer (BC). METHODS: We prospectively enrolled 99 consecutive women (median age 50 years, range 27 - 77 years) with pathologically proven stage II/III BC who underwent pretreatment FDG PET/CT. WB SUVmax, WB MTV and WB TLG were measured in all malignant lesions. Survival was analysed using the Kaplan-Meier method. Cox proportional hazards models were constructed to test for relationships among WB SUVmax, WB MTV, WB TLG, and overall survival (OS) and disease-free survival (DFS), after adjustment for age, and histopathological and immunohistochemical features (oestrogen/progesterone and HER2 expression, proliferation index and grade). RESULTS: The median values of WB SUVmax, WB MTV and WB TLG were 16.2 (range 1.5 - 33.1), 14 cm(3) (range 0.03 - 708.6 cm(3)) and 62.5 (0.06 - 3869.4), respectively. All WB semiquantitative values were higher in patients with higher TNM stage, although not significantly (all p > 0.05). The median follow-up for surviving patients was 30 months, with a range of 13 - 45 months. Both PFS and OS of patients with low WB SUVmax, WB MTV and WB TLG were longer than that of patients with high WB values for progression, although not statistically significant. However, stratifying the patients in accordance with the stage of disease, both PFS and OS were significantly lower in patients with high WB TLG and stage III than in patients with stage II (p < 0.05). In multivariate analyses, WB MTV and WB TLG were independent prognostic factors for PFS (hazard ratio 1.004, 95% confidence interval 1.002 - 1.006, p < 0.001, and hazard ratio 1.001, 95% confidence interval 1.000 - 1.001, p = 0.011, respectively). CONCLUSION: The addition of WB TLG to clinical data may provide a more detailed prediction of outcome in patients with stage III BC. Moreover, WB MTV and WB TLG are independent factors predicting recurrence of BC. On the contrary, WB SUVmax has poor prognostic significance in this cohort of patients.


Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Fluorodesoxiglucosa F18 , Terapia Neoadyuvante , Adulto , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Imagen Multimodal , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
20.
Breast Cancer Res Treat ; 146(2): 331-40, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24939059

RESUMEN

The aim of the present study was to assess the feasibility of a portable gamma camera (PGC) for guiding surgical treatment in locally advanced breast cancer (LABC) after neoadjuvant therapy (NT). Since January 2012, a PGC (Sentinella 102, ONCOVISION) has been available in our center. We planned to perform a feasibility monocentric prospective study involving 15-20 patients with LABC for assessing the diagnostic performance of this PGC after NT (Breast Cancer Surgery-S102). Before the surgical treatment and at the end of NT an injection of 99mTc-Sestamibi (100-150 MBq) was made. Conventional scintimmamography (SMM) and Sentinella 102 images were obtained from 18 patients. 10 (55.5 %) patients showed a focal uptake of tracer in the breast or lymph nodes before or after the surgical excision (on histological specimen), while 8 did not. The histological specimen concluded for a complete response to NT in 4 (22.2 %) patients and for a partial or no response to treatment in the remnant 14 subjects. The specificity and false-negative rate of the Sentinella 102 compared to SMM were 100 % for both and 38 % vs. 60 %, respectively. The global diagnostic accuracy of Sentinella 102 was: 66.7 % (95 % confidence interval: 44.88-88.44 %). The present feasibility study shows how a new nuclear imaging device can be useful in the operating theatre for guiding a radical surgery approach in patients with LABC after NT.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Cámaras gamma , Cirugía Asistida por Computador/métodos , Adulto , Anciano , Biomarcadores de Tumor , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Clasificación del Tumor , Estadificación de Neoplasias , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tecnecio Tc 99m Sestamibi , Resultado del Tratamiento
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