Neoadjuvant Chemotherapy Induces the Appearance of New Copy Number Aberrations in Breast Tumor and is Associated with Metastasis

Background: In this study, we examined the CNA-genetic landscape (CNA – copy number aberration) of breast cancer prior to and following neoadjuvant chemotherapy (NAC) and correlated changes in the tumor landscape with chemotherapy efficiency as well as metastasis-free survival. Objective: Breast cancer patients (n = 30) with luminal B molecular subtypes were treated with anthracycline- based therapy. Methods: To study CNAs in breast tumors, microarray analysis was performed. Results: Three effects of NAC on tumor CNA landscape were identified: 1 – the number of CNA-bearing tumor clones decreased following NAC; 2 – there were no alterations in the number of CNA-containing clones after NAC; 3 – the treatment with NAC increased the number of CNA-bearing clones (new clones appeared). All NAC-treated patients who had new tumor clones with amplification (20%) had a 100% likelihood of metastasis formation. In these cases, NAC contributed to the emergence of potential metastatic clones. Our study identified the following loci – 5p, 6p, 7q, 8q, 9p, 10p, 10q22.1, 13q, 16p, 18Chr and 19p – that were amplified during the treatment with NAC and may be the markers of potential metastatic clones. In other patients who showed total or partial elimination of CNA-bearing cell clones, no new amplification clones were observed after NAC, and no evidence of metastases was found with follow-up for 5 years (р = 0.00000). Conclusion: Our data suggest that the main therapeutic result from NAC is the elimination of potential metastatic clones present in the tumor before treatment. The results showed the necessity of an intelligent approach to NAC to avoid metastasis stimulation.

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Abstract PS13-45: Radiological response pattern predicts disease-free survival in breast cancer patients undergoing neoadjuvant chemotherapy

10.1158/1538-7445.sabcs20-ps13-45 ◽

2021 ◽

Author(s):

Juneyoung Ahn ◽

Tae-kyung Yoo ◽

Pill Sun Paik ◽

Min Kyung Cho ◽

Chang Ik Yoon ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Response Pattern ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

Radiological Response ◽

Disease Free

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The prognostic value of lymph node involvement after neoadjuvant chemotherapy is different among breast cancer subtypes

10.1101/2020.12.05.20244582 ◽

2020 ◽

Author(s):

Lucie Laot ◽

Enora Laas ◽

Noemie Girard ◽

Elise Dumas ◽

Eric Daoud ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Prognostic Value ◽

Lymph Node Involvement ◽

Breast Cancer Subtypes ◽

Free Survival ◽

Cancer Subtypes ◽

Node Involvement ◽

Global Population

AbstractIntroductionThe three different breast cancer subtypes (Luminal, HER2-positive and triple negative (TNBCs) display different natural history and sensitivity to treatment, but little is known about whether residual axillary disease after neoadjuvant chemotherapy (NAC) carries a different prognostic value by BC subtype.MethodsWe retrospectively evaluated axillary involvement (0, 1 to 3 positive nodes, ≥ 4 positive nodes) on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between nodal involvement (ypN) binned into 3 classes (0; [1-3];4 or more), relapse-free survival (RFS) and overall survival (OS) among the global population, and according to BC subtypes.Results1197 patients were included in the analysis (luminal (n = 526, 43.9%), TNBCs (n = 376, 31.4%), HER2-positive BCs (n = 295, 24.6%)). After a median follow-up of 110.5 months, ypN was significantly associated with RFS, but this effect was different by BC subtype (Pinteraction= 0.004), and this effect was nonlinear. In the luminal subgroup, RFS was impaired in patients with 4 or more nodes involved (HR=2.8; 95% CI [1.93;4.06], p<0.001) when compared with ypN0, while it was not in patients with 1 to 3 nodes (HR=1.24, 95% CI = [0,86;1.79]). In patients with TNBC, both 1-3N+ and ≥ 4 N+ classes were associated with a decreased RFS (HR=3.19, 95%CI= [2.05; 4.98] and HR=4.83, 95%CI= [3.06; 7.63], respectively versus ypN0, p< 0.001). Similar decreased prognosis were observed among patients with HER2-positive BC (1-3N+: HR=2.7, 95%CI= [1.64; 4.43] and ≥ 4 N+: HR=2.69, 95%CI= [1.24; 5.8] respectively, p=0.003).ConclusionThe prognostic value of residual axillary disease should be considered differently in the 3 BC subtypes to accurately stratify patients with a high risk of recurrence after NAC who should be offered second line therapies.

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Abstract P2-01-19: Long-term follow-up of the node-negative breast cancer patients before treatment evaluated with sentinel node biopsy alone following neoadjuvant chemotherapy

10.1158/1538-7445.sabcs14-p2-01-19 ◽

2015 ◽

Author(s):

Hiroko Nogi ◽

Ken Uchida ◽

Makiko Kamio ◽

Kumiko Kato ◽

Yasuo Toriumi ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Node Negative ◽

Node Biopsy ◽

Node Negative Breast Cancer ◽

Long Term Follow Up

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Randomized cooperative study of perioperative chemotherapy in breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.11.2712 ◽

1995 ◽

Vol 13 (11) ◽

pp. 2712-2721 ◽

Cited By ~ 22

Author(s):

M R Sertoli ◽

P Bruzzi ◽

P Pronzato ◽

P Queirolo ◽

D Amoroso ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Preliminary Evidence ◽

Breast Cancer Patients ◽

Free Survival ◽

Node Negative ◽

Significant Survival ◽

Significant Difference ◽

Estrogen Receptor Negative

PURPOSE The aim of this multicentric randomized trial was to determine whether reducing the interval between surgery and chemotherapy improves the outcome of breast cancer patients. PATIENTS AND METHODS Between June 1985 and July 1992, 600 breast cancer patients, clinical stages T1-3A,N0-2,M0 were randomly assigned to a perioperative cycle (PC) of cyclophosphamide 600 mg/m2, epidoxorubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF). Node-negative (N-) patients did not receive any further treatment. Node positive (N+) patients received 11 cycles if previously given PC, or 12 cycles of CEF alternated with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 (CMF). In addition, N+ patients received concomitant or sequential 5-year tamoxifen therapy. RESULTS At a median follow-up duration of 5.7 years, no significant difference in survival (88% v 84%, P = .3) between the two treatment arms was seen. However, a difference of borderline significance in relapse-free survival (RFS; 76% v 70%, P = .053) was evident. A significant survival advantage for the PC arm was detected only in the estrogen receptor-negative (ER-) patients (P = .003). RFS was significantly improved in N- patients, postmenopausal patients, and ER- patients. Multivariate analyses show that pathologic tumor size, nodal status, receptor status, and treatment (only in ER- patients) are significantly correlated with survival and RFS. PC toxicity did not influence wound healing. CONCLUSION This study provides preliminary evidence that PC positively affects relapse rate and survival in some subgroups, namely, ER- patients.

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Pharmacogenetics revisits bevacizumab in breast cancer patients: An ancillary analysis of the UCBG trial COMET—A French multicentric prospective study from R&D UNICANCER.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1079 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1079-1079

Author(s):

Gerard A. Milano ◽

Jean-Yves Pierga ◽

Jocelyn Gal ◽

Laurence Llorca ◽

Coraline Dubot ◽

...

Keyword(s):

Breast Cancer ◽

Gene Polymorphisms ◽

Low Cost ◽

Progression Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

Pcr Rflp ◽

Cox Analysis ◽

Clinical Trial Information

1079 Background: Bevacizumab (Beva) is no longer unanimously recommended in the management of breast cancer (BC). Given the absence of faithful predictors of Beva treatment outcome, we made the hypothesis that constitutional gene polymorphisms could play a role in this context. We report the pharmacogenetic ancillary study of the prospective COMET trial conducted in advanced BC patients (pts) receiving first-line Beva associated with paclitaxel. Methods: Relevant targeted gene polymorphisms were analyzed (blood) in 203 prospective pts (mean age 55.3, median follow-up 24 months). VEGFA at positions -2578C > A (rs699947), -1498T > C (rs833061), -634G > C (rs2010963), and 936C > T (rs3025039) were analyzed by PCR-RFLP. VEGFR1 319A > C (rs9582036), VEGFR2 at positions 604C > T (rs2071559), 1192C > T (rs2305948), 1416T > A (rs1870377), IL8 251T > A (rs4073), CYP2C8 139C > T (rs1572080), 399T > C (rs10509681) and ABCB1 at positions 1199 C > TA (rs2229109), 2677G > TAC (rs2032582) were analyzed by Mass-Array Agena. ABCB1 1236C > T (rs1128503) and 3435T > C (rs1045642) were analyzed by pyrosequencing. All fitted HWE. Results: Median progression-free survival (PFS) was 10.8 months. VEGFR1 319A allele was associated with longer PFS (p = 0.03). The VEGFA-1498T allele was significantly associated with both longer overall survival (OS) (p = 0.005) and PFS (p = 0.065). The VEGFA -2578C allele was associated with greater OS (p = 0.002) and PFS (p = 0.071). These two VEGFA polymorphisms were in linkage disequilibrium (p < 0.0001). Multivariate Cox analysis showed that VEGFA -2578 (p = 0.001) and VEGFR2 1416 (p = 0.025) were significant predictors of OS: the score of favorable alleles (VEGFA -2575C and VEGFR2 1416T) was highly associated with OS (p = 0.0003), with median survival at 24 months being 30% for score 0 (95%CI 15-61), 65% for score 1 (95%CI 55-75) and 90% for score 2 (95%CI 67-90). Conclusions: Application of an easy-to-perform low-cost genotyping test may identify strong predictors of Beva outcome in metastatic BC pts. In the current era of precision medicine, a pharmacogenetic-based personalized Beva therapy deserves to be prospectively validated in BC pts. Clinical trial information: 2012-A00244-39.

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Subsequent pregnancy and long-term safety from breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13575 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13575-e13575

Author(s):

Yunyeong Kim ◽

Minsun Kang ◽

Jaehun Jung ◽

Eun Kyung Cho ◽

Heung Kyu Park ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

Tumor Subtypes ◽

Study Population ◽

Disease Free

e13575 Background: Long-term safety of pregnancy after breast cancer still remained controversial, especially according to tumor subtypes. Prior results of other studies have limitations of short follow-up periods or small groups. Methods: We analyzed a population-based retrospective cohort data extracted from a random sample of 50% of women aged between 20 and 60 years who were diagnosed with breast cancer from 2002 to 2017 in the Korean National Health Insurance Service database. Propensity score matching analysis for age and Charlson Comorbidity Index (CCI) variables was performed for pregnant groups and non-pregnant groups with the same type of hormone therapy, chemotherapy and surgery. Study population was categorized to 4 biologic subgroups by the combination of hormone therapy, chemotherapy and target therapy. In this observational study, 1,566 patients with pregnancy after breast cancer were matched (1:2) to 2,462 non-pregnant patients of similar characteristics, adjusting for guaranteed bias. The matched patients were followed up to 7 years, or disease and mortality occurrence after the diagnosis of breast cancer. Survival estimates were calculated using the Kaplan-Meier analysis, groups were compared with the log-rank test. Results: Mean time from diagnosis to pregnancy was 3.4 years in study population. At a follow-up of 7 years after pregnancy, no inferiority in disease-free survival and overall survival was observed in pregnant patients factoring in treatment bias. In sub-analysis according to tumor subtypes, no difference in disease-free survival was observed between pregnant and non-pregnant patients in HR-positive and triple negative subgroup ( p= 0.088, p= 0.048, respectively). Likewise, no overall survival difference was observed in ER-positive patients and triple negative patients ( p= 0.05∼0.73, p= 0.03∼0.09, respectively). Conclusions: Our observational data provides reassuring evidence on long-term safety of pregnancy in young breast cancer patients, regardless of tumor subtypes.

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Multicenter Italian bone metastasis database: First prospective data on breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13072 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13072-e13072

Author(s):

Alberto Bongiovanni ◽

Flavia Foca ◽

Manuela Fantini ◽

Rosachiara Forcignano ◽

Fabrizio Artioli ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Bone Metastases ◽

Cancer Patients ◽

Disease Diagnosis ◽

Stage Iii ◽

Breast Cancer Patients ◽

Prospective Data ◽

Luminal B

e13072 Background: Bone Metastases (BM) are still the main cause of morbidity and morbility in cancer patients because of their complications defined as skeletal-related events (SREs).SREs reduce pts quality of life and are associated with an increasing in social and health costs. At present, data concerning BM are mainly obtained retrospectively from monocentric experiences. Methods: We performed a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 month (m)'s follow-up who were registered in a prospective BM database (BMDB). Detailed information on patients at first diagnosis of BM was recorded in a custom-built software system, updated every 6 m by participating centres and reviewed by the coordinator centre.All pts have signed an informed consent. Results: Since October 2014,618 pts with BM from solid tumors were enrolled of whom 220 have BC as primitive site with a 6 m follow-up. Median age was 62 y (range 26-86). Median Follow up was 34 m (6-149). At enrolment 109 (50%) had only BM and 109 (50%) pts had concomitant visceral and BM. Median time to first BM was 47 m (range 0-312) in Bone only disease and 78.6 m in pts with visceral bone metastases. Disease Free interval (DFI) was different according to BC molecular subtypes and stage. The univariate hazard ratio (HR) for visceral or bone metastasis was higher in luminal B tumors (1.56, 95% confidence interval [CI]:1.1-2.3) (p = 0.002), basal-like (2.50, 95% CI:1.1-6.0) (p = 0.043), and HER2-enriched tumors (1.37, 95% CI:0.78-2.4) (p = 0.273). DFI for pts with stage I disease at diagnosis of primary BC was longer than that for stage III pts (median 67.2 m, 95%CI:53.1-96.1, vs. 58.1 m, 95%CI:41.9-73.4), with a HR of 1.84 (95% CI:1.1-3.0) (p = 0.015) for the stage III group, and 0.98 (95% C.I.:0.6-1.5) (p = 0.930) for the stage II group. During BM disease, 98 pts had at least 1 SREs . Zoledronate was used in 69.1% and Denosumab in 28.3% of cases. First line treatment was hormone-based (n = 105, 50.7%) chemo-based therapy (n = 80, 38.7%) and chemo+ormono based (n = 20, 9.7%). During follow up progression disease occurred in 167 pts. Median progression-free (mPFS) and overall survival calculated from metastatic disease diagnosis (mOS) were 15.1 m (95%CI 12.6-18.4) and 66.8 m (95%CI 52.1-79.2),respectively. Conclusions: This study presents prospective data about a cohort of BC pts enrolled at the first BM occurrence and followed over the time, extrapolated by the multicentric observational BMDB in order to better understed the clinical history of breast cancer and bone metastases.

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