Total choline quantification measured by 1H MR spectroscopy as early predictor of response after neoadjuvant treatment for locally advanced breast cancer: The impact of immunohistochemical status.

BACKGROUND: Validation of new biomarkers is essential for the early evaluation of neoadjuvant treatments. PURPOSE: To determine whether measurements of total choline (tCho) by 1H spectroscopy could predict morphological or pathological complete response (pCR) of neoadjuvant treatment and whether breast cancer subgroups are related to prediction accuracy. STUDY TYPE: Prospective, nonrandomized, monocentric, diagnostic study. POPULATION: Sixty patients were initially included with 39 women participating in the final cohort. FIELD STRENGTH/SEQUENCE: A 1.5T scanner was used for acquisition and MRS was performed using the syngo GRACE sequence. ASSESSMENT: MRS and MRI examinations were performed at baseline (TP1), 24-72 hours after first chemotherapy (TP2), after the end of anthracycline treatment (TP3), and MRI only after the end of taxane treatment (TP4). Early (EMR) and late (LMR) morphological response were defined as %ΔDmax13 or %ΔDmax14, respectively. Responders were patients with %ΔDmax >30. Pathological complete response (pCR) patients achieved a residual cancer burden score of 0. STATISTICAL TESTS: T-test, receiver operating characteristic (ROC) curves, multiple regression, logistic regression, one-way analysis of variance (ANOVA) analysis were used for the analysis. RESULTS: At TP1 there was a significant difference between response groups for tCho1 concerning EMR prediction (P = 0.05) and pCR (P < 0.05) and for Kep 1 (P = 0.03) concerning LMR prediction. At TP2, no modification of tCho and other parameters could predict response. At TP3, ΔtCho, ΔDmax, and ΔVol could predict LMR (P < 0.05 for all parameters), pCR (P < 0.05 for all parameters), and ΔKtrans could predict only pCR (P = 0.04). Logistic regression at baseline showed the highest area under the curve (AUC) of 0.9 for prediction of pCR. The triple negative (TN) subgroup showed significantly higher tCho at baseline (P = 0.02) and higher ΔtCho levels at TP3 (P < 0.05). DATA CONCLUSION: Baseline measurements of tCho in combination with clinicopathological criteria could predict non-pCR with a high AUC. Furthermore, tCho quantification for prediction of pCR was more sensitive for TN tumors. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;48:982-993.

Quantitative DCE-MRI for prediction of pathological complete response following neoadjuvant treatment for locally advanced breast cancer: the impact of breast cancer subtypes on the diagnostic accuracy.

OBJECTIVES: To assess whether DCE-MRI pharmacokinetic (PK) parameters obtained before and during chemotherapy can predict pathological complete response (pCR) differently for different breast cancer groups. METHODS: Eighty-four patients who received neoadjuvant chemotherapy for locally advanced breast cancer were retrospectively included. All patients underwent two DCE-MRI examinations, one before (EX1) and one during treatment (EX2). Tumours were classified into different breast cancer groups, namely triple negative (TNBC), HER2+ and ER+/HER2-, and compared with the whole population (WP). PK parameters Ktrans and Ve were extracted using a two-compartment Tofts model. RESULTS: At EX1, Ktrans predicted pCR for WP and TNBC. At EX2, maximum diameter (Dmax) predicted pCR for WP and ER+/HER2-. Both PK parameters predicted pCR in WP and TNBC and only Ktrans for the HER2+. pCR was predicted from relative difference (EX1 - EX2)/EX1 of Dmax and both PK parameters in the WP group and only for Ve in the TNBC group. No PK parameter could predict response for ER+/HER-. ROC comparison between WP and breast cancer groups showed higher but not statistically significant values for TNBC for the prediction of pCR CONCLUSIONS: Quantitative DCE-MRI can better predict pCR after neoadjuvant treatment for TNBC but not for the ER+/HER2- group. KEY POINTS: • DCE-MRI-derived pharmacokinetic parameters can predict response status of neoadjuvant chemotherapy treatment. • Ktrans can better predict pCR for the triple negative group. • No pharmacokinetic parameter could predict response for the ER+/HER2- group.

Integrative proteomic and gene expression analysis identify potential biomarkers for adjuvant trastuzumab resistance: analysis from the Fin-her phase III randomized trial.

Trastuzumab is a remarkably effective therapy for patients with human epidermal growth factor receptor 2 (HER2)--positive breast cancer (BC). However, not all women with high levels of HER2 benefit from trastuzumab. By integrating mRNA and protein expression data from Reverse-Phase Protein Array Analysis (RPPA) in HER2-positive BC, we developed gene expression metagenes that reflect pathway activation levels. Next we assessed the ability of these metagenes to predict resistance to adjuvant trastuzumab using gene expression data from two independent datasets.10 metagenes passed external validation (false discovery rate [fdr] < 0.05) and showed biological relevance with their pathway of origin. These metagenes were further screened for their association with trastuzumab resistance. An association with trastuzumab resistance was observed and validated only for the AnnexinA1 metagene (ANXA1). In the randomised phase III Fin-her study, tumours with low levels of the ANXA1 metagene showed a benefit from trastuzumab (multivariate: hazard ratio [HR] for distant recurrence = 0.16[95%CI 0.05-0.5]; p = 0.002; fdr = 0.03), while high expression levels of the ANXA1 metagene were associated with a lack of benefit to trastuzmab (HR = 1.29[95%CI 0.55-3.02]; p = 0.56). The association of ANXA1 with trastuzumab resistance was successfully validated in an independent series of subjects who had received trastuzumab with chemotherapy (Log Rank; p = 0.01).In conclusion, in HER2-positive BC, some proteins are associated with distinct gene expression profiles. Our findings identify the ANXA1metagene as a novel biomarker for trastuzumab resistance.

Metastatic breast carcinoma confined to bone: portrait of a clinical entity.

BACKGROUND: The current study was performed to study metastatic breast carcinoma that remains confined to bone. METHODS: The medical notes of 2514 breast carcinoma patients who were treated in 2 academic units over a 20-year period were screened and patients who fulfilled the following criteria were selected: 1) clinical manifestation and imaging confirmation of bone metastases, and 2) metastatic disease remaining confined to bone for a minimum of 24 months. Available clinical and pathologic data were recorded and analyzed. The objective of the current study was to describe this clinical entity and investigate possible correlations between clinicopathologic parameters and clinical outcome. RESULTS: A total of 104 patients (4% of the total screened patient population) fulfilled the study criteria. The majority of patients were postmenopausal, with a median age of 58 years; 44 of the patients were found to have metastases at the time of presentation (M1) and 60 patients developed metastases at a median of 38 months (range, 8-160 months) after surgery for the primary tumor. Metastases remained confined to bone for a median of 50 months. Survival after the diagnosis of bony metastases was 72 months and was similar in the 2 groups (66 months vs. 78 months). Of the patients treated, 80% responded to hormonal therapy, and 76.5% responded to chemotherapy. There was no association noted between survival and tumor grade, anatomic distribution, or disease extension. CONCLUSIONS: Bone-confined metastatic breast carcinoma has an indolent clinical course that alleviates the need for vigorous follow-up and calls into question aggressive therapeutic approaches in these patients. Translational studies are warranted to map the molecular profile, leading to the development of targeted therapies in this group of patients.