Classical lobular breast carcinoma consistently lacks <i>topoisomerase‐IIα</i> gene amplification: implications for the tailored use of anthracycline‐based chemotherapies

Brunello, Eleonora; Brunelli, Matteo; Manfrin, Erminia; Nottegar, Alessia; Bersani, Samantha; Vergine, Marco; Molino, Annamaria; Fiorio, Elena; Chilosi, Marco; Gobbo, Stefano; Martignoni, Guido; Bonetti, Franco

doi:10.1111/j.1365-2559.2011.04067.x

Cited by 12 publications

(9 citation statements)

References 24 publications

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“…The same was reported in a different study from our group, analyzing DTC-status 3 years after diagnosis [12]. In this previous study it was also observed that DTC-positivity was positively associated with lobular carcinoma, which can be explained by a relative resistance also to the anthracycline-containing chemotherapy [25,30]. Our study supports the selection of higher stage patients into future DTC intervention trials (Table 1), in order to select those with both the traditionally highest risk of relapse and the highest frequency of DTC-positivity.…”

Section: Discussionsupporting

confidence: 79%

Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study

et al. 2012

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BackgroundPresence of disseminated tumor cells (DTCs) in bone marrow (BM) after completion of systemic adjuvant treatment predicts reduced survival in breast cancer. The present study explores the use of DTCs to identify adjuvant insufficiently treated patients to be offered secondary adjuvant treatment intervention, and as a surrogate marker for therapy response.MethodsA total of 1121 patients with pN1-3 or pT1c/T2G2-3pN0-status were enrolled. All had completed primary surgery and received 6 cycles of anthracycline-containing chemotherapy. BM-aspiration was performed 8-12 weeks after chemotherapy (BM1), followed by a second BM-aspiration 6 months later (BM2). DTC-status was determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. If DTCs were present at BM2, docetaxel (100 mg/m2, 3qw, 6 courses) was administered, followed by DTC-analysis 1 month (BM3) and 13 months (BM4) after the last docetaxel infusion.ResultsClinical follow-up (FU) is still ongoing. Here, the descriptive data from the study are presented. Of 1085 patients with a reported DTC result at both BM1 and BM2, 94 patients (8.7%) were BM1 positive and 83 (7.6%) were BM2 positive. The concordance between BM1 and BM2 was 86.5%. Both at BM1 and BM2 DTC-status was significantly associated with lobular carcinomas (p = 0.02 and p = 0.03, respectively; chi-square). In addition, DTC-status at BM2 was also associated with pN-status (p = 0.009) and pT-status (p = 0.03). At BM1 28.8% and 12.8% of the DTC-positive patients had ≥2 DTCs and ≥3 DTCs, respectively. At BM2, the corresponding frequencies were 47.0% and 25.3%. Of 72 docetaxel-treated patients analyzed at BM3 and/or BM4, only 15 (20.8%) had persistent DTCs. Of 17 patients with ≥3 DTCs before docetaxel treatment, 12 patients turned negative after treatment (70.6%). The change to DTC-negativity was associated with the presence of ductal carcinoma (p = 0.009).ConclusionsAfter docetaxel treatment, the majority of patients experienced disappearance of DTCs. As this is not a randomized trial, the results can be due to effects of adjuvant (docetaxel/endocrine/trastuzumab) treatment and/or limitations of the methodology. The clinical significance of these results awaits mature FU data, but indicates a possibility for clinical use of DTC-status as a residual disease-monitoring tool and as a surrogate marker of treatment response.Trial registrationClin Trials Gov NCT00248703

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Section: Discussionsupporting

confidence: 79%

Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study

et al. 2012

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“…Invasive lobular carcinoma patients may potentially benefit less from chemotherapy based on the high‐rate of ER positivity, low mitotic index, and other biomarkers . There is reason to speculate, however, that ILC patients might strongly benefit from adjuvant endocrine therapy since the overwhelming majority of ILC tumors express ER.…”

Section: What Is the Optimal Methods Of Evaluation For Disease Extent mentioning

confidence: 99%

Issues Affecting the Loco-regional and Systemic Management of Patients with Invasive Lobular Carcinoma of the Breast

et al. 2016

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Invasive lobular carcinoma (ILC) of the breast is the second most common type of invasive breast carcinoma accounting for 8-14% of all breast cancers. Traditional management of ILC has followed similar paradigms as that for invasive ductal carcinoma (IDC). However, ILC represents a pathologically, clinically and biologically unique variant of breast cancer with particular management challenges. These challenges are seen in both the loco-regional management of ILC; where ILC tumors tend to avoid detection and hence present as more clinically advanced and surgically challenging carcinomas, and the systemic management with a unique response pattern to standard systemic therapies. Because of these challenges, the outcome for patients with ILC has likely lagged behind the continued improvements seen in outcome for patients with IDC. Here, we discuss some of the unique challenges ILC presents and discuss possible management strategies to best overcome the difficulties in the loco-regional and systemic management of patients with ILC.

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“…• Inverse correlation with tumor grade Brunello et al), suggesting the rationale for the anthracyclines chemotherapy resistance. Indeed, TOPO2A gene amplification was shown to be a good predictor of response to anthracyclines (35).…”

Section: Cicline D1mentioning

confidence: 99%

Invasive lobular breast cancer: critical issues and emerging options

Furlanetto¹

2014

RIO

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Invasive lobular carcinoma represents a unique entity of breast cancer with peculiar pathological and clinical features, which are different to the more common invasive ductal carcinoma. Indeed, emerging evidences suggest differences in both the metastatic and recurrence pattern and, above all, in the treatment sensitivity, with particular regard to chemotherapy. Nevertheless, the treatment decision of invasive lobular carcinoma is based upon data as a subgroup of trials where the large majority of patients were affected by a different histology. In this review, an overview of the literature about invasive lobular carcinoma is provided, aiming to investigate the role of emerging predictive and prognostic factors and to analyze the new therapeutic opportunities.

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Classical lobular breast carcinoma consistently lacks topoisomerase‐IIα gene amplification: implications for the tailored use of anthracycline‐based chemotherapies

Abstract: In the era of personalized and tailored therapies, we suggest that patients affected by the classical lobular subtype of breast carcinoma constantly lack the ad hoc predictive rationale for receiving common chemotherapy that includes anthracyclines.

Cited by 12 publications

References 24 publications

Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study

Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study

Issues Affecting the Loco-regional and Systemic Management of Patients with Invasive Lobular Carcinoma of the Breast

Invasive lobular breast cancer: critical issues and emerging options

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