The 2012 IMPAKT task force investigated the medical usefulness of current methods for the classification of breast cancer into the ‘intrinsic’ molecular subtypes (luminal A, luminal B, basal-like and ...HER2). A panel of breast cancer and/or gene expression profiling experts evaluated the analytical validity, clinical validity and clinical utility of two approaches for molecular subtyping of breast cancer: the prediction analysis of microarray (PAM)50 assay and an immuno-histochemical (IHC) surrogate panel including oestrogen receptor (ER), HER2 and Ki67. The panel found the currently available evidence on the analytical validity and clinical utility of Ki67 based on a 14% cut-off and PAM50 to be inadequate. The majority of the working group members found the available evidence on the analytical validity, clinical validity and clinical utility of ER/HER2 to be convincing. The panel concluded that breast cancer classification into molecular subtypes based on the IHC assessment of ER, HER2 and Ki67 with a 14% cut-off and on the PAM50 test does not provide sufficiently robust information to modify systemic treatment decisions, and recommended the use IHC for ER and HER2 for the identification of clinically relevant subtypes of breast cancers. Methods for breast cancer classification into molecular subtypes should, however, be incorporated into clinical trial design.
Adipose tissue releases angiogenic factors that may promote tumour growth.
To determine whether body mass index (BMI), subcutaneous fat area (SFA) and visceral fat area (VFA) are associated with ...outcomes in patients given first-line bevacizumab-based treatment for metastatic colorectal cancer (MCC). Patients CT was used to measure SFA and VFA in 120 patients with MCC who received bevacizumab-based treatment (bevacizumab group, n=80) or chemotherapy alone (chemotherapy group, n=40) as first-line treatment. Associations linking BMI, SFA and VFA to tumour response, time-to-progression (TTP) and overall survival (OS) were evaluated.
In the bevacizumab group, median follow-up lasted for 24 months (3-70). BMI, SFA and VFA values above the median (ie, high BMI, high VFA and high SFA) were significantly associated with absence of a response. TTP was shorter in patients with high BMI (9 vs 12 months; p=0.01) or high VFA (9 vs 14 months; p=0.0008). High VFA was associated with shorter OS (p=0.0493). By multivariate analysis, high VFA was independently associated with response, TTP and OS (HR=7.18, p=0.008, HR=5.79, p=0.005 and HR=2.88, p=0.027, respectively). In the chemotherapy group, median follow-up lasted for 30 months (4-84). BMI, SFA and VFA were not associated with response, TTP or OS. In the whole population, interaction between VFA and bevacizumab administration was significant for response (OR=3.31, p=0.005) and TTP (HR=1.64, p=0.022), thereby confirming the results.
This study provides the first evidence that high VFA independently predicts a poorer outcome in patients given first-line bevacizumab-based treatment for MCC. However, this predictive biomarker needs to be validated in a different dataset.
Breast cancer diagnosed during pregnancy (BCP) is rare, but the prevalence is expected to rise. Long-term follow-up data regarding this clinically challenging condition are scarce. The main objective ...of this multicentre case-control French study was to compare the survival between pregnant patients and matched controls.
Patients from 27 centres diagnosed between 2000 and 2009 with histologically proven invasive breast cancer occurring during pregnancy were retrospectively included. Controls were matched to BCP patients on age, clinical T stage, hormone receptor, HER2, administration of neo-adjuvant chemotherapy and pathological node involvement in the absence of neo-adjuvant chemotherapy. Five-year overall survival (OS), disease-free survival (DFS) and metastasis-free survival (MFS) rates were estimated using the Kaplan–Meier method.
One hundred and eleven BCP patients and 253 controls were included. Median age was 33 and 35 years, respectively. Both populations were managed similarly, except for less frequent sentinel node dissection (p = 0.026) and taxane administration (p = 0.03) among BCP patients. Median follow-up was 7.5 years. Survival rates were similar between both BCP and control patients: 5-year OS rates were 83.1% (95% CI: 74.5–89.0) vs 85.5% (95% CI: 80.4–89.4), respectively, p = 0.31; 5-year DFS rates 60.0% (95% CI: 50.1–68.6) vs 68.5% (95% CI: 62.3–73.9), respectively, p = 0.12 and 5-year MFS rates 71.0% (95% CI: 61.3–78.6) and 74.5% (95% CI: 68.6–79.5), respectively, p = 0.21.
Our study showed that the survival outcomes of patients diagnosed with BCP were not significantly different as compared to those of matched non-pregnant controls. A proper management of women diagnosed with BCP is crucial.
•Pregnancy at the time of breast cancer diagnosis was not associated with worse outcomes.•According to IHC classification, the prognosis was the same in both groups.•Proper management of women diagnosed with breast cancer during pregnancy is crucial.
Purpose
In LOTUS (NCT02162719), adding the oral AKT inhibitor ipatasertib to first-line paclitaxel for locally advanced/metastatic triple-negative breast cancer (aTNBC) improved progression-free ...survival (PFS; primary endpoint), with an enhanced effect in patients with
PIK3CA/AKT1/PTEN
-altered tumors (FoundationOne next-generation sequencing NGS assay). We report final overall survival (OS) results.
Methods
Eligible patients had measurable previously untreated aTNBC. Patients were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status, and were randomized 1:1 to paclitaxel 80 mg/m
2
(days 1, 8, 15) plus ipatasertib 400 mg or placebo (days 1–21) every 28 days until disease progression or unacceptable toxicity. OS (intent-to-treat ITT, immunohistochemistry PTEN-low, and PI3K/AKT pathway-activated NGS
PIK3CA/AKT1/PTEN
-altered populations) was a secondary endpoint.
Results
Median follow-up was 19.0 versus 16.0 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively. In the ITT population (
n
= 124), median OS was numerically longer with ipatasertib–paclitaxel than placebo–paclitaxel (hazard ratio 0.80, 95% CI 0.50–1.28; median 25.8 vs 16.9 months, respectively; 1-year OS 83% vs 68%). Likewise, median OS favored ipatasertib–paclitaxel in the PTEN-low (
n
= 48; 23.1 vs 15.8 months; hazard ratio 0.83) and
PIK3CA/AKT1/PTEN
-altered (
n
= 42; 25.8 vs 22.1 months; hazard ratio 1.13) subgroups. The ipatasertib–paclitaxel safety profile was unchanged.
Conclusions
Final OS results show a numerical trend favoring ipatasertib–paclitaxel and median OS exceeding 2 years with ipatasertib–paclitaxel. Overall, results are consistent with the reported PFS benefit; interpretation within biomarker-defined subgroups is complicated by small sample sizes and TNBC heterogeneity.
Abstract Purpose To assess the interobserver reproducibility of the quantification of the visceral and subcutaneous fat by computed tomography from an umbilical slice and study the effect of the ...level of the slice (slice going through the navel versus a slice going through disc L3–L4). Materials and methods Forty-four breast cancer patients who had a CT-scan were included in this study. This is a double blind (junior versus senior) retrospective study to determine the interobserver reproducibility. A junior observer studied the variation between two levels of slice by selecting an image going through L3–L4 and the navel. Results The measurement of the fat obtained from an umbilical slice seemed to be well correlated and consistent with that obtained from a slice with a disc reference (L3–L4). The interobserver reproducibility is good for the quantification of the umbilical fat (Spearman and Lin at 0.9921 and 0.985 P < 0.001 for the visceral fat). Conclusion The interobserver reproducibility of the single slice CT-scan measurement going through the navel (easily detected) is excellent and may therefore be used in oncology as a predictive tool to measure a characteristic of the host and not the tumor.
Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors for some of which the epithelial growth factor receptor (EGFR) pathway may play an important role. We investigated the efficacy ...and toxicity of an anti-EGFR antibody (panitumumab) combined with a standard neoadjuvant anthracycline–taxane-based chemotherapy in patients with operable, stage II–III, TNBC.
Treatment in this multicentric neoadjuvant pilot study consisted of panitumumab (9mg/kg) for eight cycles q.3 weeks combined with four cycles of 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC100: 500/100/500mg/m2) q.3 weeks, followed by four cycles of docetaxel (T: 100mg/m2) q.3 weeks. Following therapy, all patients underwent surgical resection. Pathologic complete response (pCR) in assessable patients was the main end point while clinical response, toxicity and ancillary studies were secondary end points. Paraffin-embedded and frozen tumor samples were systematically collected with the aim to identify predictive biomarkers of efficacy and resistance in order to select biologically defined subpopulations for potential further clinical development of the anti-EGFR antibody.
Sixty patients were included with 47 assessable for pathologic response. The pCR rates were 46.8% 95% confidence interval (CI): 32.5% to 61.1% and 55.3% 95% CI: 41.1% to 69.5% according, respectively, to Chevallier and Sataloff classifications. The complete clinical response (cCR) rate was 37.5%. Conservative surgery was carried out in 87% of cases. Toxicity was manageable. The association of high EGFR and low cytokeratin 8/18 expression in tumor cells on one hand and high density of CD8+ tumor-infiltrating lymphocytes on the other hand were significantly predictive of pCR.
Panitumumab in combination with FEC100 followed by docetaxel appears efficacious, with acceptable toxicity, as neoadjuvant therapy of operable TNBC. Several biomarkers could help define large subsets of patients with a high probability of pCR, suggesting a potential interest to further develop this combination in biologically defined subgroups of patients with TNBC.
NCT00933517.
The estimated rate of de novo metastatic breast cancer (dnMBC) at the time of diagnosis is between 5 to 12%. International guidelines recommend metastatic work-up (MWU) only in women with advanced ...breast cancer. The purpose of this study was to describe the characteristics and prognosis of patients with dnMBC diagnosed without an initial indication for MWU.
We conducted a retrospective, comparative study in dnMBC patients selected from the ESME-MBC cohort. Patients were treated in France between 2008 and 2016. We compared two populations: patients in whom dnMBC was diagnosed by staging although not indicated by guidelines (non-guideline staging NGS) and those in whom dnMBC was diagnosed by guideline staging (GS).
During the study period, 22,463 patients with MBC were included in the ESME cohort. Among them, 6698 were dnMBC patients. In 247 of these patients (6% of dnMBC and 1% of the overall population), dnMBC was diagnosed by non-guideline staging. Women in this group were significantly younger (57 vs. 59 years, p = 0.02) and had fewer metastatic sites at diagnosis than dnMBC-GS patients. The two groups were not significantly different in terms of the other characteristics. Overall survival (OS) and progression-free survival (PFS) were better in the dnMBC-NGS group than in the dnMBC-GS group. The impact on survival was confirmed by univariate and multivariate analysis (HR 1.83 1.31–2.57, p < 0.01).
This study provides the first description of a very specific population. These patients with dnMBC-NGS were younger and more likely to have oligometastatic disease with a better prognosis.
•T1/T2 N0 de novo metastatic breast cancer (MBC) represented 6% of all de novo MBC.•Metastatic diagnosis in this population implied an unrecommended workup.•These patients were younger with oligometastatic disease and had a better prognosis.•Locoregional therapy prior to diagnosis in this population did not change survival.
We analysed whether the level of human epidermal growth factor receptor-2 (HER-2) amplification significantly influenced either pathological complete response (pCR) or recurrence-free survival (RFS) ...and overall survival (OS) after trastuzumab-based neoadjuvant therapy.
In all, 99 patients with an HER-2-amplified breast tumour treated with trastuzumab-based neoadjuvant therapy were included. Tumours were classified as low amplified (LA; 6-10 signals per nuclei) or highly amplified (HA; >10 signals). Pathological response was assessed according to Chevallier's classification (pCR was defined as grade 1 or 2). Median follow-up lasted 46 months (6-83). Cox uni- and multivariate analyses were performed.
In all, 33 tumour samples were LA and 66 were HA. The pCR in HA tumours was significantly higher than in LA tumours (55% vs 24%, P=0.005), whereas no association was found between the pCR rate and tumour stage, grade or hormone receptor status. In multivariate analysis, the pathological nodal status (P=0.005) and adjuvant trastuzumab (P=0.037) were independently associated with RFS, whereas the level of HER-2 amplification nearly reached statistical significance (P=0.057). There was no significant difference between LA and HA tumours for OS (P=0.22, log-rank).
The level of HER-2 gene amplification significantly influenced pCR but not RFS or OS in non-metastatic breast cancer treated with trastuzumab-based neoadjuvant therapy. However, RFS in patients with HA tumours tended to be shorter.
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