Predicting response to neoadjuvant chemotherapy in nonmetastatic hormone receptor-positive breast cancer using 21-gene Breast Recurrence Score test.

e12093 Background: The Recurrence Score (RS) result based on the 21-gene Oncotype DX Breast Recurrence Score assay is standard of care in deciding adjuvant chemo-hormonal therapy versus hormone therapy alone in hormone-receptor positive (HR+), HER 2 negative, node–negative breast cancer. This study explores the role of RS result in predicting the response to neoadjuvant chemotherapy (NACT). Methods: In this retrospective single institution cohort study, electronic medical records of 148 women with HR+, HER 2 negative, non-metastatic breast cancer who received NACT from 2006 onward were screened. 38 patients were excluded due to lack of tissue for testing. Pretreatment biopsy blocks were sent to Genomic Health, Inc. for Oncotype Dx testing. Low RS result was defined as ≤25. Pathologic complete response (pCR) was defined as no residual tumor. Partial response (PR) was residual tumor with > 25% decrease in the largest dimension. No response (NR) was defined as < 25% decrease in the tumor post NACT. Progression (PD) was defined as increase in size of original tumor or new site(s) of disease. Results: Of the 110 patients studied, 58% were postmenopausal women. Fifty percent were African American, 12% were Caucasian and 27% were Hispanic. Invasive ductal carcinoma was the predominant histology (86%). Most patients had > T2 disease (97%) with 73% being clinically node positive. Adriamycin based NACT regimen was used in treating 86.3% of the women. Forty patients (36.4%) had tumor with RS≤25. NR/PD was significantly higher in tumors with RS≤25 (27/40) vs RS > 25 (13/70) (OR: 9.1, 95% CI: 3.7-22.2, P< 0.001). pCR was seen in 16% with RS > 25 and 0% with RS ≤25. Response to NACT (pCR/PR) was 32.5% in RS≤25 vs 81.4% in RS > 25. In tumors with response, RS > 25 was associated with a greater percent decrease in the tumor size compared to RS≤25 (median decrease of 71% vs 52%, P= 0.033). Conclusions: HR+, HER 2 negative, RS≤25 breast cancer is associated with increased rates of NR/PD and is unlikely to respond to NACT. Recurrence Score result determination in pretreatment breast cancer biopsy samples can be an effective tool to select patients with non-metastatic breast cancer for NACT. Studies are needed to determine novel neoadjuvant therapeutic approaches in patients who are candidates for neoadjuvant therapy but are unlikely to benefit from NACT.

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Abstract PS5-37: The feasibility of obtaining oncotype DX breast recurrence score®results from metastatic sites of patients with hormone receptor positive metastatic breast cancer

10.1158/1538-7445.sabcs20-ps5-37 ◽

2021 ◽

Author(s):

Julie Anne L Gemmill ◽

Patricia Thompson ◽

Rebecca Batiste ◽

Caterina Vacchi-Suzzi ◽

Christina Preece ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Hormone Receptor ◽

Metastatic Breast ◽

Recurrence Score ◽

Oncotype Dx ◽

Hormone Receptor Positive ◽

Metastatic Sites ◽

Breast Recurrence

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Real world experience of palbociclib in hormone receptor-positive metastatic breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18094 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18094-e18094 ◽

Cited By ~ 2

Author(s):

Faizan Malik ◽

Naveed Ali ◽

Syed Imran Mustafa Jafri ◽

Mark L. Sundermeyer ◽

Michael Jeffrey Seidman ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Side Effects ◽

Real World ◽

Hormone Receptor ◽

Objective Response ◽

Metastatic Breast ◽

Hormone Receptor Positive ◽

Her 2 ◽

Grade 3

e18094 Background: Palbociclib has been approved as a first line therapy in hormone-receptor positive (HR+) and HER-2 negative metastatic breast cancer(MBC) manifesting significant improvement in progression free survival (PFS). We studied this drug in a community setting. The endpoints were estimated PFS, objective response, toxicities and patient outcomes. Methods: This was a single-center, retrospective study of HR+MBC patients receiving palbociclib after its FDA approval. 22 patients were selected Results: A total of 22 patients were included (Male = 2, Female = 20). Median age was 60-years (range, 49-84). About 90% patients had received at least one previous therapy and the median number was 1.5. 13% patients were on fulvestrant, 86% on letrozole and 4.5% on exemestane. About 64% of patients had ECOG status of ≥ 1. Median duration of palbociclib treatment was 5-months, therefore, an estimated PFS at 18-months was 50%. 4.5% patients attained complete response. 22% patients achieved partial response, 22% had stable disease and 50% patients demonstrated disease progression. 72% patients had neutropenia, of which 45% were grade ≥ 3. Thrombocytopenia and anemia were common (63% and 58%, respectively) but grade ≥ 3 thrombocytopenia or anemia was not observed. 50% patients required dose reductions and 18% required drug cessation owing to side effects. Conclusions: PFS was much lower as compared to actual trials in our real-world experience. Despite, several interesting observations were good objective response rates in males and HER-2+ patients underscoring its potential clinical efficacy in these subsets. Furthermore, apart from myelosuppressive side effects, pneumonitis was observed in one patient necessitating vigilance in clinical practice

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Response to neoadjuvant chemotherapy and the 21-gene breast recurrence score in young women with estrogen receptor-positive early breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.514 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 514-514

Author(s):

Tal Sella ◽

Shari I. Gelber ◽

Philip Daniel Poorvu ◽

Hee Jeong Kim ◽

Yaileen D Guzman Arocho ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Neoadjuvant Chemotherapy ◽

Young Women ◽

Recurrence Score ◽

High Grade ◽

Gene Assay ◽

Estrogen Receptor Positive ◽

Breast Recurrence ◽

Response To Neoadjuvant Chemotherapy

514 Background: The 21- gene Breast Recurrence Score predicts benefit from adjuvant chemotherapy in estrogen receptor positive (ER+), HER-2 negative (-) breast cancer (BC). We aimed to examine whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NAC). Methods: We identified patients with stage I-III ER+/HER2− BC treated with NAC from the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤ 40 years. The 21-gene assay was performed on tumor specimens removed prior to NAC either as part of clinical care or retrospectively for research. Pathologic complete response (pCR) was defined as no residual invasive tumor (ypT0/is ypN0). The relationship between Recurrence Score result (RS) and pCR was evaluated using logistic regression modeling. Results: 76 women in the cohort had undergone NAC for ER+, HER2- BC and were eligible for this analysis: 5 had undergone clinical 21-gene assay testing, 71 had banked specimens retrospectively tested. Median age at diagnosis was 36.7 (24.3-40). Most tumors were of ductal histology (78%), high grade (51%), progesterone receptor (PgR) positive (86%), ≥T2 (88%), clinically node positive (74%), and anthracycline and taxane containing protocols were administered in 86% of cases. RS ranged between 5-75 with 50% > 25 and only 4 < 11. Mean RS was significantly higher among tumors achieving pCR vs. non-pCR response (51.9 vs. 26.6, pwilcoxon= 0.0005). pCR rate in patients with RS > 25 was 21% (8/38) vs. 5% in patients with RS < 25 (2/38), with both pCRs in the <25 group in patients with RS 21-25. In univariable analysis, PgR negativity (odds ratio (OR) 5.62, 95% confidence interval (CI) 1.27-24.89, p = 0.02), high grade (OR 9.03, 95%CI 1.07-76.32, p = 0.04) and higher RS as a continuous variable (OR 1.08, 95%CI 1.04-1.13, p = 0.0003) were associated with a greater likelihood of pCR. In multivariable analysis only RS remained significantly associated with pCR (OR: 1.07, 95%CI 1.01-1.12, p = 0.01): a 7% increase in the odds of pCR for every 1-point increase in RS. Conclusions: In young women with ER+, HER2- BC who received NAC, higher pretreatment RS was associated with an increased likelihood of pCR. Genomic expression profiling assays may have a role in decision-making in young women in need of neoadjuvant therapy. For women with low likelihood of benefiting from NAC, alternative approaches are clearly warranted. Given the demonstrated efficacy of neoadjuvant endocrine therapy in post-menopausal women, further evaluation in young women should be pursued.

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Optimal regimen for treatment-naive hormone receptor-positive HER-2 negative metastatic breast cancer

Future Oncology ◽

10.2217/fon-2018-0086 ◽

2019 ◽

Vol 15 (2) ◽

pp. 105-107

Author(s):

Burak Bilgin ◽

Mehmet AN Şendur ◽

Mutlu Hızal ◽

Muhammed Bülent Akıncı ◽

Didem Şener Dede ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Hormone Receptor ◽

Metastatic Breast ◽

Hormone Receptor Positive ◽

Treatment Naïve ◽

Her 2 ◽

Optimal Regimen

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Quality of Life in Hormone Receptor–Positive HER‐2 + Metastatic Breast Cancer Patients During Treatment with Letrozole Alone or in Combination with Lapatinib

The Oncologist ◽

10.1634/theoncologist.2010-0012 ◽

2010 ◽

Vol 15 (9) ◽

pp. 944-953 ◽

Cited By ~ 17

Author(s):

Beth Sherrill ◽

Mayur M. Amonkar ◽

Bintu Sherif ◽

Julie Maltzman ◽

Lisa O'Rourke ◽

...

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Hormone Receptor ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Hormone Receptor Positive ◽

Her 2

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4-gene score to predict response to neoadjuvant chemotherapy, metastasis, and survival.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12592 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12592-e12592

Author(s):

Masanori Oshi ◽

Eriko Katsuta ◽

Li Yan ◽

Itaru Endo ◽

Kazuaki Takabe

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Metastatic Breast ◽

Breast Cancer Dataset ◽

Gene Score ◽

Cancer Dataset ◽

Predictive Values ◽

Study Results ◽

Response To Neoadjuvant Chemotherapy

e12592 Background: At this point, there is no treatment to cure metastatic breast cancer. On the other hand, improvement of treatment of metastatic breast cancer is the key to further improve breast cancer survival. One possible opportunity is to detect metastatic breast cancer in it’s “early” phase when it many respond to treat such as immune therapy. We hypothesized that a scoring system generated from metastatic clone predict metastasis and survival. Methods: A gene signature score was generated using differentially expressed genes between MDA-MB-231 human breast cancer cell-line and its highly metastatic variant, LM2-4, and TCGA breast cancer dataset. METABRIC cohort as well as six neoadjuvant therapeutic cohorts and four metastatic cohorts were used as validation cohort. The totals of 4,199 samples from a large number of cohorts were analyzed in the study. Results: Among the 297 genes that were up-regulated in LM2-4, tumor expression of four genes had the strongest association with disease-free survival in TCGA breast cancer dataset (hazard ratio [HR] > 1.2 with p < 0.02). A 4-gene score calculated from the combined expression of these genes correlated with overall survival in TCGA data, with HR of 1.44 (95% confidence interval [CI] = 1.52-2.98; p < 0.001). The association of higher scores with worse survival was also observed for disease-specific survival in the METABRIC breast cancer cohort (HR = 1.57, 95% CI = 1.23-1.72, p < 0.001). Tumors with high score enriched gene sets related with cancer aggressiveness such as E2F, G2F, MYC v1 and v2 (FDR = 0.23, 0.19, 0.20, 0.21, respectively), whereas those with lower score enriched estrogen response pathway related set (FDR = 0.13) in TCGA and it was validated with METABRIC cohorts. We also found that the score associated with distant metastasis to brain or lung (p < 0.001). Kaplan-Meier analyses of site-specific metastasis-free interval demonstrated that for all three cohorts, patients with high scores had significantly increased risk for development of metastasis to the lung (p≤0.02). This association of the score with metastasis risk was also seen for brain for two cohorts, and it was seen for bone in one cohort. Importantly, we found that the high score group had a higher pCR rate than the low score group for especially ER+/HER2- breast cancer in two cohorts (p = 0.003 and p = 0.004). And the score significantly decreases with good response to neoadjuvant chemotherapy (p = 0.022) or hormonal therapy (p = 0.013). Conclusions: This novel gene score may be clinically useful with both prognostic and predictive values for breast cancer.

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