Search

Breast cancer is heterogeneous in clinical, morphological, immunohistochemical and biological features, as reflected by several different prognostic subgroups. Neoadjuvant approaches are currently used for the "in vivo" efficacy assessment of treatments. Pathological complete response (pCR) has been reported as a reliable predictive factor of survival in that setting. However, pCR remains a subject of controversy in terms of definition and its evaluation methods. In addition, its predictive value for patient outcome in various breast cancer biological subtypes has been under debate. In this review, we will present the existing definitions of pCR, the impact of its evaluation methods on its rate and the assessment of its predictive value for patient outcome in the molecular subtypes of breast cancer (luminal A and B, Triple Negative and HER2-positive).

Objective: Neoadjuvant chemotherapy (NACT) allows for a more frequent use of breast-conservative surgery; it is also an in vivo model of individual tumor sensitivity which permits to determine new prognostic factors to personalize the therapeutic approach. Methods: Between 2000 and 2012, 318 patients with primary invasive breast cancer were treated with a median of 6 cycles of NACT; they received either an anthracycline-based FEC 100 protocol (31.1%), or anthracyclines + taxanes (53.5%), with trastuzumab if indicated (15.4%). Results: After a median follow-up of 44.2 months, the pathological complete response rate according to the classification of Chevallier et al. [Am J Clin Oncol 1993;16:223-228] was 19.3%, and overall (OS) and disease-free survival (DFS) at 10 years were 60.2 and 69.6%, respectively. Univariate analyses demonstrated that the Residual Disease in Breast and Nodes (RDBN) index was the most significant prognostic factor for OS (p = 0.0082) and DFS (p = 0.0022), and multivariate analyses mainly revealed that the residual tumor size, residual involved node number and post-chemotherapy Scarff-Bloom-Richardson (SBR) grading were the most significant prognostic factors. Conclusions: In a cohort of patients who were all homogeneously treated with some of the most common drugs for breast cancer, we demonstrate that NACT may provide additional prognostic factors and confirm the RDBN index. As this index allows for the prediction of survival with different breast cancer subtypes, we suggest that it should be calculated routinely to help clinicians to select patients who need adjuvant treatments.

Numerous studies have demonstrated that a significant change in weight during chemotherapy treatment was a factor of poor prognosis in early breast cancer women. However, the causes and mechanisms involved in this phenomenon are not fully known. This review summarizes current knowledge about the causes of energy imbalance during chemotherapy treatment and the mechanisms that have been proposed as responsible for the increased risk of relapse and death in this population. Current preventive strategies focus on physical activity programs but also on the use of metformin during and after chemotherapy.

Purpose of the study: In a new database harbouring the patients of several prospective phase II neoadjuvant trials (fec 50–100, net, tncf, taxotere/tncf, taxotere alone), the predictive value of tumour factors (SBR grade, RH, Her2, Ki-67 and cycline D1) was studied in 466 women with stage II-III operable breast cancer treated between 1991 and 2006. Patients and methods: Median age of the patients was 48 years [27-76]. Median diameter of the invasive tumour was 40 mm [10-130]. 382 (82%) patients had a canalar, 57 (12.2%) a lobular, 14 (3%) a mixed or invasive carcinoma, 3 (0.6%) neoplasic cells only and 10 (2.2%) another carcinoma. Before chemotherapy, 33% were grade III SBR. The median number of NCT courses was 6 [1-8] followed by a surgery for 98%, a radiotherapy for 93%, an adjuvant chemotherapy (20%) and/or a hormonotherapy (56%). Results: Overall response rate was 73% (18% complete). The complete pathological response (pCR) rate was 17.2% according to Chevallier's classification. On 455 patients operated, 324 (71%) had a conservative surgery. On 390 patients with an axillary dissection, 195 (50%) had involved nodes (median number: 2 [1-20]). After a median follow-up of 135 months, DFS and actuarial survival at 120 months were 61.9% and 73%, respectively. After chemotherapy, we found a significant variation for SBR grade ***: there was five fold more patients for whom we observed a down grading of the SBR grade (grade 2/3 to grade 1) than up grading (grade 1 to grade 2/3), p=6.1.10−6. For patients in objective response, we observed a significant decrease of SBR grade (p=1.7.10−3). Moreover, the variation of SBR grade was also pronostic. Indeed, the disesase-free survival for patients who presented a SBR down grading after chemotherapy was significantly better (p=0.031) compared to patients for whom SBR grade remained stable or was in up grading. There was a tendancy for overall survival (p=0.15). Conclusion: Down grading of SBR grade appears linked to response and so may constitute a parameter of better prognostic. At the opposite, up grading of SBR grade is an adverse prognostic factor. To conclude, it is interesting to emphasize that SBR grade variations can be assessed when patients are not in pCR, ie plays a complementary role. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-20.

Author Summary Background. Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment. Methods. Overall, 264 previously untreated stage II–III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m2, respectively, for 3 cycles) followed by docetaxel (100 mg/m2 for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by Results. Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses. Conclusion. Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected.

Numerous studies have demonstrated that a significant change in weight during chemotherapy treatment was a factor of poor prognosis in early breast cancer women. However, the causes and mechanisms involved in this phenomenon are not fully known. This review summarizes current knowledge about the causes of energy imbalance during chemotherapy treatment and the mechanisms that have been proposed as responsible for the increased risk of relapse and death in this population. Current preventive strategies focus on physical activity programs but also on the use of metformin during and after chemotherapy.

e11526 Background: Everolimus, in combination with exemestane, is indicated to treat hormone receptor-positive, HER2-negative metastatic breast cancer (MBC), in postmenopausal women without symptom...

e11615 Background: Gene expression studies have demonstrated that breast cancer can be divided into three major subgroups : Luminal, Human Epidermal Growth Factor Receptor-2 (HER2) over-expression and Oestrogen negative (ER-). Luminal breast cancer is well known for its better prognosis compared with the other types. Conversely, response is less effective by pCR criteria after chemotherapy. This work aimed to evaluate if pCR could still be considered as a surrogate marker in luminal subgroup according to immunohistochemical classification : Hormonal receptor positive and HER2 negative (HR+HER2-). Methods: All 132 luminal early breast cancer patients treated by neo-adjuvant chemotherapy (NAC), in our institution from 2001 to 2007 were included in this study. NAC treatment comprised anthracycline alone, taxotere alone or sequential use of these two drugs. Survival curves have been established according to the Kaplan-Meier’s method. Comparison of curves were performed in using Log-rank test. The median of follow-up was 102 months (range 59 – 142 months) in October 2012. Results: Median age was 53.5 (range 34–78) years and median initial tumor size was 4cm (range 1-10). Objective response rate was 65% (86 patients), of which 8% (10 patients) had a complete response after 6 courses. One hundred and six (80%) underwent breast conservation surgery. Seven patients (5%) and ten patients achieved pCR (8%) according to Chevallier and Satatloff’s classification, respectively. Twenty patients did relapse and 18 patients died. At 10 years, Disease-free survival (DFS) and overall survival (OS) rate was 81% and 84%, respectively. All pCR patients, regardless of classification, did not relapse. However, the patients who achieved a pCR had not a significant difference in DFS and OS compared to the patients who did not. Conclusions: pCR was not a surrogate marker after a relatively short survey of 100 months for luminal breast cancers, who have generally late relapses. However, sixty five percent of patients had >50% reduction in primary tumor and 80% of patients had a breast conservation. Further studies are needed to identify new markers able to predict patients’ survival.

Background In breast cancer, positive Hormone Receptors (HR) constitute a favourable prognostic factor whereas HER-2 overexpression is an adverse prognostic factor associated with a more aggressive tumor. In a retrospective database of 282 breast cancer patients diagnosed from 1991 to 2006, we analysed the overall survival (OS) and the disease-free survival (DFS) of 4 phenotypes: HR-/HER-2- (triple negative, TN); HR + /Ki-67 20% or Her2+ (luminal B) and HER-2 overexpression (HER-2 + /HR-). Patients and methods Median diameter of the invasive tumour was 40 mm [10-130]. 231 (82%) patients had a canalar carcinoma. 33% of the tumours were grade III SBR. Patients received either an anthracycline-based chemotherapy (47%), a taxane-based chemotherapy (21%) or a combination of both (32%). The median number of NCT courses was 6 [1-8] followed by a surgery for 97.6%, a radiotherapy for 93%, an adjuvant chemotherapy for 20% and/or an hormonotherapy for 56%. Only 5 patients received adjuvant herceptin for 1 year. In the different subgroups, we had 123 luminal A tumors (44%), 67 luminal B tumours (24%), 21 Her2+ tumours (7%) and 71 TN tumours (25% of patients). Results According to tumour's phenotype, the pCR (Chevallier's classes 1 + 2) was: 3.3% for luminal A, 16.6%, for luminal B, 33.3% for Her2+ HR- and 26% for triple negative tumours. On 2 April 2012, the median follow-up was 148 months (range, 63- 252). We evaluated the OS and the DFS in the four subgroups, at 10 years. -For TN: OS and DFS were 58.5% and 56.2%. -For luminal A: OS and DFS were 76.1% and 64.7%. -For luminal B: OS and DFS were 81.7% and 72.4%. -For Her2 + HR- subgroup: OS and DFS were 64.5% and 56.4%. pCR is an objective method improvement after NCT, but it is variable among subsets, and may constitute an acquired prognostic factor. However, it was much smaller in hormonal-positive tumors subsets and may there not be an endpoint per se. We observed a significant improvement of DFS and OS for patients who reached a pCR only in TN breast cancer. However Her2 subset may be too small to reach significance here. Conclusion OS and DFS were better in luminal A and B subgroups. Conversely OS and DFS decreased for TN and Her2+ subtypes. When TN breast cancer patients reached a pCR, OS and DFS were significantly improved. Disclosure All authors have declared no conflicts of interest.

Purpose: As a contribution to the discussion of pathological complete response (pCR) as surrogate end-point, after neo-adjuvant chemotherapy (NACT), we studied disease-free survival (DFS) and overall survival (OS) at 15 years with THP-doxorubicin, vinorelbine, 5-Fluorouracil and cyclophosphamide (TNCF regimen). Patients and methods: This retrospective cohort study has been done in 61 patients treated with neo-adjuvant semi-intensive chemotherapy. PCR rate was analysed separately in breast (no histological evidence of invasive tumor cells and / or presence of in situ carcinoma tumor cells) and in nodes (no metastasis). Univariate and multivariate analysis (COX regression) have been used to assess the potential prognostic factors with a median follow up of 13.8 years. Results: Thirty two patients relapsed and 21 died. At 15 years, DFS and OS were 53% and 88% respectively for the patients who achieved pCR compared to 33% and 53% respectively for those who did not achieve pCR. Multivariate analysis with COX model showed that pCR in breast and the number of involved nodes at surgery were 2 factors who can significant predict patients’ DFS and these two factors were significantly related. Conclusion: In this current study, pCR in breast can be used as surrogate marker to predict survival outcome, even with a long-term follow-up of 15 years. When pathological response was incomplete in primary tumor, the number of involved nodes (n > 4 vs n Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2707. doi:1538-7445.AM2012-2707

1121 Background: Metastatic breast cancer (MBC) is an incurable disease in most cases; then treatment is palliative, to prolong overall survival (OS) and control clinical symptoms. Progressively the figures obtained have improved with time. However, the optimal duration of therapy is unknown. Few authors have considered the treatment globally versus for each line and fewer have demonstrated the interest of chemotherapy (CT) after the third line. The aim of this study was to assess tumoral response and OS of patients treated with more than 3 lines of treatment, for each line given. We selected recent patients treated during “taxanes/anti-aromatase era (TAA)” corresponding to an important progress in breast cancer therapy. Methods: Our metastatic database recorded 590 patients with MBC. Among these patients, 530 received at least one line of CT and 383 an hormonotherapy (HT). TAA was defined from December 31th, 1993, as from this date they became available for the french patients. Results: Median OS surviva...

1133 Background: Achieving pathologic complete response (pCR) is the main goal in NACT. PCR rates will be studied comparatively for stage II-IIIA operable breast cancer in 264 women, randomized to receive either 3 FEC 100 then 3 docetaxel 100 mg/m2 (standard arm A) or adapted arm B beginning with 2 FEC 100. Docetaxel will be given if tumor size decreased by less than 30 or 50 percent after 2 or 4 FEC 100, respectively; otherwise FEC100 was given for 6 courses before surgery. A new classification will assess the limited residual disease in breast and nodes (LRDBN) when obtained. Methods: 140 patients, all Her 2 negative with or without HR on microbiopsies, have been randomized to date with a median age of 52 years. They were repartited according to 2 tumour phenotypes : Her2-HR+ (luminal phenotype) and Her2-HR- (TN). 107 patients post NACT were operated. Pathological response was analyzed in 98 BC (77 Luminal; 18 TN) according to: Chevallier’s (Am J Clin oncol 1993), Sataloff’s (J Am Coll Surg 1995) and Re...