Giulia Bianchi

Axillary lymph node dissection versus no dissection in patients with T1N0 breast cancer: A randomized clinical trial (INT09/98)

Although axillary surgery is still considered to be a fundamental part of the management of early breast cancer, it may no longer be necessary either as treatment or as a guide to adjuvant treatment. The authors conducted a single‐center randomized trial (INT09/98) to determine the impact of avoiding axillary surgery in patients with T1N0 breast cancer and planning chemotherapy based on biological factors of the primary tumor on long‐term disease control.

18F-FLT PET/CT as an imaging tool for early prediction of pathological response in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy: a pilot study

PurposeWe evaluated whether 18F-3′-deoxy-3′-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT).MethodsIn this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results.ResultsAt baseline, median of maximum standardized uptake values (SUVmax) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUVmax and Ki67 proliferation rate index was significant (r = 0.69, p < 0.001). Analysis of the relative percentage change of SUVmaxin the primary tumour (∆SUVTmax(t1)) and axillary nodes (∆SUVNmax(t1)) after the first NCT cycle showed that the power of ∆SUVTmax(t1) to predict pCR + RCB I responses (AUC = 0.91, p < 0.001) was statistically significant, whereas ∆SUVNmax(t1) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVTmax(t1) > −52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score μ based on ΔSUVTmax(t1) and ΔSUVNmax(t1) parameters is proposed.ConclusionThe preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population need to be validated in a larger independent cohort.

Predictive biomarkers in the treatment of HER2-positive breast cancer: an ongoing challenge

The transmembrane tyrosine kinase receptor HER2 is overexpressed in 20% of invasive breast cancers and is associated with more aggressive disease. Until the advent of targeted agents, HER2 was associated with worse outcome. Trastuzumab, a recombinant humanized anti-HER2 monoclonal antibody, combined with chemotherapy improves disease-free and overall survival in both primary and metastatic tumors and represents a foundation of care for patients with HER2-positive breast cancers. However, a sizeable number of patients do not respond to this reagent, indicating the need for a biomarker able to recognize resistant tumors. Here, we review various studies on mechanisms of action and resistance to trastuzumab that have proven relevant in understanding how tumor care can be tailored to all HER2-positive patients.

Metastatic breast cancer treated with lapatinib with a prolonged benefit: a case report and a review of therapeutic options available.

A 53-year-old woman was treated, after trastuzumab progression of HER2-positive metastatic disease, with capecitabine plus lapatinib and subsequently with lapatinib alone. To date, she has had persistent remission of disease since 2009.

Trastuzumab and Hypofractionated Whole Breast Radiotherapy: A Victorious Combination?

Micro‐Abstract Radiotherapy (RT) and trastuzumab are usually administered concurrently in patients with human epidermal growth factor receptor‐2‐positive breast cancer. Adjuvant hypofractionated RT, delivered in 15 or 16 fractions, has been accepted as a valid alternative to standard fractionation. We examined the feasibility of associating hypofractionated RT with trastuzumab, finding a safe profile in terms of acute skin and cardiac toxicity. Introduction: The purpose of this study was to examine the impact of trastuzumab on acute skin and cardiac toxicity in patients with breast cancer treated with chemotherapy with or without trastuzumab and adjuvant whole breast hypofractionated radiotherapy (hypo‐RT). Materials and Methods: The study was conducted on 727 patients treated from April 2009 to October 2016. Patients received 42.4 Gy in 16 daily fractions (2.65 Gy per fraction). A boost was only administered in cases with grade (G) 3 primary tumor and close or positive margins. Acute and late toxicity was assessed prospectively during and after hypo‐RT, based on the Radiation Therapy Oncology Group scale. Multivariable logistic regression models were used to examine the onset of acute skin toxicity (≥ G2) in the whole study population, and the impact of trastuzumab on the onset of acute skin (≥ G2) or cardiac toxicity in the subgroup of 176 patients given chemotherapy. Results: A total of 176 patients received chemotherapy with anthracycline and taxane, and 51 (29%) of them were also treated with trastuzumab. Acute G1, G2, and G3 skin toxicity occurred, respectively, in 56.8%, 27.3%, and 1.1% of the patients given chemotherapy alone, and in 64.7%, 19.6%, and 0% of those given trastuzumab as well. Among the patients given chemotherapy, left ventricular ejection fraction (LVEF) toxicity developed with a severity of G1 (LVEF < 60%‐50%) in 12 (6.8%) patients, G2 (LVEF < 50%‐40%) in 2 (1.1%) patients, and G3 (LVEF < 40%) in 1 (0.6%) patient. Among the patients also given trastuzumab, 7 (13.7%) patients had G1 LVEF toxicity, and 1 (2%) patient had G2 LVEF toxicity. We found that patients given trastuzumab were at higher risk of cardiac toxicity ≥ G1 (odds ratio, 4.3; P = .01), and at lower risk of acute skin toxicity ≥ G2 (odds ratio, 0.4; P = .03) than patients given chemotherapy alone. Conclusions: This analysis showed that trastuzumab with adjuvant hypo‐RT for patients with breast cancer was generally well‐tolerated in routine clinical practice. A longer follow‐up will be necessary to assess late cardiac toxicity.

Evaluation of Local Oncologic Safety in Nipple–Areola Complex-sparing Mastectomy After Primary Chemotherapy: A Propensity Score-matched Study

Background: Nipple–areola complex‐sparing mastectomy (NSM), extending the concept of skin‐sparing mastectomy, allows for the provision of a better cosmetic result. Large operable T2‐T3 breast cancer might theoretically appear suitable for this surgical option as an alternative to conventional mastectomy or breast‐conserving surgery, when a good response to primary chemotherapy has been achieved. Patients and Methods: From January 2009 to May 2013, 422 patients with invasive breast cancer were progressively accrued to NSM. Of the 422 patients, 361 underwent NSM as first‐line treatment (NSM group), and 61 underwent surgery after primary chemotherapy (NSM‐PC group). A total of 151 breast cancer patients, who had undergone PC and conventional total mastectomy (TM‐PC group) from 2004 to 2009 were evaluated as comparative group with respect to the NSM‐PC group. Using propensity score matching, local disease‐free survival (LDFS) was evaluated comparatively. Results: The rate of nipple–areola involvement in the NSM and NSM‐PC groups was 13.3% and 9.8%, respectively (P = .539). The nipple–areola involvement in the NSM and NSM‐PC groups was significantly associated with the tumor size (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.13–1.95; P = .004), plurifocal or pluricentric tumor (OR, 3.18; 95% CI, 1.72–5.89; P < .001), and the presence of an intraductal component (OR, 2.38; 95% CI, 1.22–4.64; P = .011). The LDFS in the NSM‐PC and TM‐PC matched cohorts did not show a significant difference, with a 4‐year LDFS of 0.89 (95% CI, 0.77–0.95) and 0.93 (95% CI, 0.83–0.97), respectively (hazard ratio [HR], 1.31; 95% CI, 0.40–4.35; P = .655). The NSM‐PC cohort was also compared with the NSM cohort in terms of LDFS using 2 different matching criteria, with the tumor size before and after neoadjuvant chemotherapy as the balancing covariate. In the first of the 2 comparisons, the hazards of local relapse were comparable between the 2 matched groups (HR, 1.23; 95% CI, 0.37–4.04; P = .739). In the second comparison, the NSM‐PC patients showed a significant greater hazard of local relapse than did the NSM patients (HR, 3.60; 95% CI, 1.10–11.80; P = .035). Conclusion: NSM might be a valuable option for large breast cancer treated by primary chemotherapy. The rate of local relapse seemed to be related to the disease stage, and no significant association with the type of surgery was detected. Micro‐Abstract: After primary chemotherapy, large operable T2‐T3 breast cancers might be suitable for nipple–areolar complex‐sparing mastectomy (NSM). Using propensity score analysis, NSM did not show an increased risk of local recurrence compared with conventional mastectomy. The risk of local recurrence was associated with the stage of disease before primary chemotherapy.

Prognosis of women with early breast cancer and PIK3CA mutations

We read the article “Factors related to incomplete treatment of breast cancer in Kumasi, Ghana.” The authors found that religion type, believing in traditional treatments, and lack of awareness of national health insurance coverage were the factors for ceasing the treatment [1]. A randomized controlled study assessed the factors related to coping strategies for women completing breast cancer treatment, which were not evaluated in this article. They reported that positive problem solving, escape/avoidance, and seeking social support were the significant factors [2]. Moreover, the authors commented that Islamic women were focused on fatalism, and they did not complete the treatment because many physicians were male. If these statements were true, then the Islamic womenwould not have chosen surgical treatment or would not have been operated on by male surgeons, relevant issues that were not reported in the study.

Different biological and prognostic breast cancer populations identified by FDG-PET in sentinel node-positive patients: Results and clinical implications after eight-years follow-up

BACKGROUND Sentinel node (SN) biopsy is the standard method to evaluate axillary node involvement in breast cancer (BC). Positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (FDG-PET) provides a non-invasive tool to evaluate regional nodes in BC in a metabolic-dependent, biomolecular-related way. In 1999, we initiated a prospective non-randomized study to compare these two methods and to test the hypothesis that FDG-PET results reflect biomolecular characteristics of the primary tumor, thereby yielding valuable prognostic information. PATIENTS AND METHODS A total of 145 cT1N0 BC patients, aged 24-70 years, underwent FDG-PET and lymphoscintigraphy before surgery. SN biopsy was followed in all cases by complete axillary dissection. Pathologic evaluation in tissue sections for involvement of the SN and other non-SN nodes served as the basis of the comparison between FDG-PET imaging and SN biopsy. RESULTS FDG-PET and SN biopsy sensitivity was 72.6% and 88.7%, respectively, and negative predictive values were 80.5% and 92.2%, respectively. A subgroup of more aggressive tumors (ER-GIII, Her2+) was found mainly in the FDG-PET true-positive (FDG-PET+) patients, whereas LuminalA, Mib1 low-rate BCs were significantly undetected (p = 0.009) in FDG-PET false-negative (FDG-PET-) patients. Kaplan-Meier survival estimates after a median follow-up of more than 8 years showed significantly worse overall survival for FDG-PET+ patients in node-positive (N+) patients (p = 0.035) as compared to N+/FDG-PET- patients, which overlapped with survival curves of N- and FDG-PET+ or - patients. CONCLUSIONS Our findings suggest that FDG-PET results reflect intrinsic biologic features of primary BC tumors and have prognostic value with respect to nodal metastases. FDG-PET false negative cases appear to identify less aggressive indolent metastases. The possibility to identify a subgroup of N+ BC patients with an outcome comparable with N- BC patients could reduce the surgical and adjuvant therapeutic intervention.

Correction: Everolimus (EVE) and exemestane (EXE) in patients with advanced breast cancer aged ≥ 65 years: new lessons for clinical practice from the EVA study

BACKGROUND The present analysis focuses on real-world data of Everolimus-Exemestane in advanced HR+ve, HER2-ve elderly breast cancer patients (aged 65 years) included in the EVA study, with unique findings in those aged 70 years. METHODS Data are collected from clinical records and analysed according to age cut-off (< 65 years; 65 - 69 years and {greater than or equal to} 70 years). Relationship of analyzed variables with response were tested by mean of a Mantel-Haenszel chi square test. Time to event analysis was described by Kaplan Meier approach and association with baseline characteristics was analysed by stratified log-rank test and proportional hazard model. RESULTS From July 2013 to December 2015, the EVA study enrolled overall 404 pts. 154 patients out of 404 (38,1%) were aged {greater than or equal to} 65 years, of whom 87 were {greater than or equal to} 70 years. Median duration of EVE treatment was 28.5 weeks (95% CI 19.0 - 33.8) in patients aged 65-69 years and 24,4 weeks (95% CI 19,2 - 33,2) in those aged {greater than or equal to} 70 years. Fewer patients aged 65 years received the highest EVE Dose-Intensity (>7.5 mg/day) in comparison to younger patients (49,6% vs. 66,8%). Grade 3–4 toxicities occurred to 55 patients (35,7%), mainly stomatitis (10,9%), rash (5,8%) and non-infectious pneumonitis (NIP) (3,6%). Some toxicities, such as weight loss and anaemia were peculiarly observed in patients aged {greater than or equal to} 70 years. Five treatment-related deaths were collected (3,2%). CONCLUSIONS EVE-EXE combination remains one of the potential treatments in HR+ patients also for elderly ones.

Surgery for Locally Recurrent Breast Cancer

Local recurrences in breast cancer after breast-conserving surgery or mastectomy represent two completely different oncological events. Mastectomy is still considered the gold standard of treatment in patients with ipsilateral breast tumour recurrence (IBTR) after breast-conserving surgery and postoperative standard radiotherapy. However there has recently been interest in second conservative surgery for these women although as yet there are no data to prove the oncologic safety of this approach. In cases of a second breast-conserving surgery, interstitial brachytherapy is the most widely applied technique of adjuvant radiotherapy, with some technical variants, including low, pulsed or high dose rate administration. Reconstructive surgery for locally recurrent breast cancer is a challenge, due to the previous irradiation and scarring of the tissues. In case of salvage mastectomy for locally recurrent cancer after breast-conserving surgery, implant-based breast reconstruction may be difficult, with a high rate of complications due to previous adjuvant radiotherapy. In many cases, autologous flap reconstruction, from the abdomen or from the back, may be the first or the only reconstructive option for patients who develop local recurrence following earlier breast-conserving therapy. Full skin- or nipple-sparing surgery in these cases is also challenging and often associated with wound or nipple necrosis, again due to previous irradiation. Local recurrences after mastectomy have an earlier clinical presentation and slightly different risk factors, compared to IBTR after breast-conserving surgery. A multidisciplinary approach is required for optimal management of local recurrence after mastectomy. Patients with locally recurrent breast cancer after previous mastectomy and implant reconstruction are generally offered wide excision, if surgically possible. Patients must be informed about possible long-term complications of postoperative radiotherapy, and autologous reconstruction may be the best option to reduce local short- and long-term complications. The type of axillary restaging in cases of isolated local recurrence, with previous sentinel node biopsy and without gross nodal metastases at the time of local recurrence, has been widely debated. The rate of detection and removal of re-operative sentinel nodes is substantially lower than those of sentinel nodes for the primary tumour, even though repetition of sentinel node biopsy is technically safe, feasible and accurate. Finally, in all cases of local recurrence, full restaging should be undertaken before planning treatment.