- Email: [email protected]
Multi-gene prognostic signatures and prediction of pathological complete response of ER-Positive HER2-negative breast cancer patients to neo-adjuvant chemotherapy
abstracts Conclusions: SC significantly decreases AMH and AFC values independently of chemotherapeutic agents in patients with BC. The low AMH levels and less AFC before SC may predict CIA. _ Legal entity responsible for the study: Istanbul Demiroglu Bilim University. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
255P
Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy
Background: Triple negative breast cancers are a heterogeneous group of breast cancer candidate to adjuvant chemotherapy in a large majority of cases. However, literature data indicate that the diagnosis of special types of breast cancer might be associated with a different outcome if compared with invasive ductal carcinoma with similar biological features and stages. Selected triple negative apocrine breast cancer can have an extremely good prognosis. Methods: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated between January 1998 and December 2016 at European Institute Oncology, Milan, we identified 24 patients with pT1-pT2, node-negative, triple negative subtype and Ki-67 20% who did not receive adjuvant chemotherapy. We compared the outcome of this cohort with a similar group of 48 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features (matching ratio 1:2). Results: The median age was 63 and 50 years in the apocrine and ductal group, respectively. The mean value of Ki-67 expression was 12% in the apocrine group and 14% in the ductal group. 83% of apocrine tumors had size less than 2 cm, compared with 71% of ductal tumors. After a median follow-up of 6.6 years no patients in the apocrine group experienced a breast cancer related event compared with 12 events (including 5 loco-regional recurrences, 3 distant recurrences e 4 contralateral tumors) in the ductal carcinoma group (Gray test p-value¼0.015). Conclusions: The outcome of selected apocrine triple negative breast cancer patients is excellent and possibly deserves a treatment de-escalation. Multicenter projects focusing on the possibility to avoid adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: G. Cancello: Honoraria (self): Pierre Fabre. E. Montagna: Honoraria (self): Pierre fabre; Honoraria (self): gentili. E. Munzone: Honoraria (institution), Advisory / Consultancy: Pierre Fabre; Honoraria (institution), Advisory / Consultancy: Genomic Health. S. Dellapasqua: Travel / Accommodation / Expenses: Roche. M.A. Colleoni: Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Advisory / Consultancy: OBI Pharma; Advisory / Consultancy: Puma Biotechnology; Advisory / Consultancy: Celldex; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.
256P
Novel blood based circulating tumour cell biomarker for breast cancer detection
C.-Y. Liu1, Y.-F. Tsai1, F.-M. Lin2, J.-C. Wu2, Y.-S. Lin1, T.-C. Chao1, K.-L. King1, P.-J. Lien1, J. Wang1, Y.-H. Lin1, Y.-C. Lai1, H.B. Hsieh2, A. Saklecha2, J.-M. Lai2, S.-E. Chang3, M. Javey3, D. Watson3, R. Mei2, L.-M. Tseng1 1 Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei, Taiwan, 2 R&D, CellMax Life, Sunnyvale, CA, USA, 3Clinical Affairs, CellMax Life, Sunnyvale, CA, USA
CI: 78.2%, 95.6%) sensitivity was 56.3% (95% CI: 43.3%, 68.6%) for the most common subtype ER/PRþHER2-, 36.4% (17.2%-59.3%) for HER2þ, 43.8% (19.8%- 70.1%) for TNBC, 46.5% (37.1%- 56.1%) overall. Sensitivity was 62.5% (35.4%- 84.8%) for late stage (Stage III/IV cancer) and 43.5% (33.2%- 54.2%) for early stage (Stage 0, I or II cancer) patients. In the subset of 41 individuals with an indeterminate classification of BIRADS 3 (likely benign) or BIRADS 4 (likely malignant) sensitivity was 90% and specificity was 47.6% (95% CI: 25.7%, 70.2%). Conclusions: In this initial study, CTC was a significant predictor of cancer. The CTC assay can easily be combined with cfDNA to enhance detection rates. Proof-of-concept data suggests potential for a rule out test to avoid unnecessary follow-up/biopsies in BIRADS 3/4 patients. Legal entity responsible for the study: CellMax Life. Funding: CellMax Life. Disclosure: F. Lin: Shareholder / Stockholder / Stock options: CellMax Life. J. Wu: Shareholder / Stockholder / Stock options: CellMax Life. H.B. Hsieh: Shareholder / Stockholder / Stock options: CellMax Life. S. Chang: Shareholder / Stockholder / Stock options: CellMax Life. M. Javey: Shareholder / Stockholder / Stock options: CellMax Life. D. Watson: Shareholder / Stockholder / Stock options: CellMax Life. R. Mei: Shareholder / Stockholder / Stock options: CellMax Life. All other authors have declared no conflicts of interest.
257P
C. Mazo1,2,3, S. Barron3, C. Mooney1, W.M. Gallagher3,4 UCD School of Computer Science, University College Dublin, Dublin, Ireland, 2CeADAR: Centre for Applied Data Analytics Research, Dublin, Ireland, 3OncoMark Limited, Dublin, Ireland, 4UCD School of Biomolecular & Biomedical Science, UCD Conway Institute, Dublin, Ireland 1
Background: Determining which early stage breast cancer patients should receive chemotherapy is an important clinical and economic issue. Chemotherapy has many adverse side effects, impacting on quality of life, along with significant economic consequences. Biomarkers that can predict patient response to chemotherapy can help avoid ineffective overtreatment. The aim of this work is to assess if the OncoMasTR (OM) signature can predict pathological complete response (pCR) to neo-adjuvant chemotherapy, and to compare its predictive value with EndoPredict (EP) and Oncotype DX (RS). Methods: Gene expression datasets derived from breast cancer patients that had pretreatment biopsies, received neo-adjuvant chemotherapy and an assessment of pCR were obtained from GEO (GSE16716, GSE20271, GSE25066, GSE32646, GSE34138, GSE41998, GSE22226). Patients with ER-positive, HER2-negative disease and pCR data were selected. OM, EP and RS numeric risk scores were approximated by applying the gene coefficients to the corresponding mean probe expression values. Association with pCR was estimated using logistic regression. Results: A total of 813 patients with 66 pCR events were included in the analysis. OM, EP and RS prognostic scores were moderately well correlated according to the Pearson’s correlation coefficient: OM vs EP (min¼0.44; mean¼0.67; max¼0.81), OM vs RS (min¼0.34; mean¼0.62; max¼0.79), and RS vs EP (min¼0.55; mean¼0.79; max¼0.89). Significant predictors of pCR with p-values of 0.0001 for all three signatures. Odds ratios for a 1 standard deviation increase in risk score, adjusted for cohort, were similar in magnitude and not significantly different: OM 1.66 (1.29 to 2.16), EP 1.76 (1.37 to 2.27), RS 1.84 (1.44 to 2.35). Conclusions: In this in silico analysis, OM, EP and RS prognostic scores were significantly predictive of pCR to neo-adjuvant chemotherapy in ER-positive, HER2-negative breast cancer. Optimal stratification for neo-adjuvant chemotherapy offers the opportunity for personalised care, improved therapy response rates, and reduced ineffective treatment and costs. Legal entity responsible for the study: University College Dublin. Funding: The EI and from the European Union’s Horizon 2020 research and innovation programme under the Marie Slodowska-Curie grant agreement No. 713654. Disclosure: The author has declared no conflicts of interest.
258P Background: There is an unmet need for a blood test to detect breast cancer in women with dense breast tissue or clinically aggressive subtypes that may be missed by mammograms. Cell-free DNA in blood has shown 15-58% sensitivity for breast cancer. We evaluated the performance of a circulating tumor cell (CTC) assay as a complimentary biomarker for detecting breast cancer in an Asian population, which has high incidence of dense breast tissue. Methods: A single-center, IRB-approved, prospective and blinded clinical study was conducted on 114 Taiwanese females with biopsy-confirmed breast cancer, and 50 healthy controls confirmed by ultrasound or mammogram. Four milliliter of blood was collected prior to imaging and processed using the CellMax biomimetic platform (CMx) which enumerates CTCs utilizing selection criteria based on a set of markers (cytokeratin 18, mammaglobin, CD45), cell morphometry (size, N/C ratio) and nucleus morphology. Logistic regression models for CMx CTC counts and patient age were used to assess the classification performance of the CMx test. Results: Of the 114 cancer (80% were stage 02), the subtypes were confirmed for 102 (62% ER/PRþ HER2-, 22% HER2þ, 16% TNBC). CTC count was a significant predictor of cancer status (Likelihood Ratio P-value ¼ 0.0001). At 90% specificity (exact 95%
v86 | Breast Cancer, Early Stage
Multi-gene prognostic signatures and prediction of pathological complete response of ER-Positive HER2-negative breast cancer patients to neo-adjuvant chemotherapy
Impact of menopause status on breast cancer outcomes and amenorrhea incidence during adjuvant tailored dose dense chemotherapy
A. Papakonstantinou1, A. Matikas1, M. Hellstro¨m2, H. Johansson2, G. Steger3, R. Greil4, S. Loibl5, M. Gnant6, V. Moebus7, M. Untch8, T. Foukakis1, J. Bergh1 1 Department of Oncology-Pathology, Karolinska Institutet - Bioclinicum, Stockholm, Sweden, 2CKC, Karolinska University Hospital-Solna, Stockholm, Sweden, 3Medical Oncology, Austria and Gaston H. Glock Research Center, Medical University, Vienna, Austria,4Medical Department, Paracelsus Medical University, Salzburg, Austria, 5German Breast Group, Neu-Isenburg, Germany, 6Department of Surgery, Medical University of Vienna, Vienna, Austria, 7Department of Gynecology and Obstetrics, Klinikum Frankfurt Ho¨chst, Academic Hospital Goethe University, Frankfurt, Germany, 8Clinic for Gynecology, Gynecologic Oncology and Obstetrics, Helios Klinikum Berlin Buch, Berlin, Germany Background: Adjuvant dose-dense chemotherapy improves breast cancer (BC) outcomes compared to standard chemotherapy, with no increase in chemotherapy-
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.081/5576387 by guest on 26 October 2019
G. Cancello1, E. Montagna1, E. Pagan2, V. Bagnardi2, E. Munzone1, S. Dellapasqua1, M. Iorfida1, M. Mazza1, A.P. De Maio1, G. Viale3, G. Mazzarol3, P. Veronesi4, V. Galimberti1, G. Santomauro1, M.A. Colleoni5 1 Division Of Medical Senology, Istituto Europeo di Oncologia, Milan, Italy, 2Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy, 3 Division of Pathology, Istituto Europeo di Oncologia, Milan, Italy, 4Senology, Istituto Europeo di Oncologia, Milan, Italy, 5International Breast Cancer Study Group, Division of Medical Senology, Istituto Europeo di Oncologia, Milan, Italy
Annals of Oncology
255P
Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy
Background: Triple negative breast cancers are a heterogeneous group of breast cancer candidate to adjuvant chemotherapy in a large majority of cases. However, literature data indicate that the diagnosis of special types of breast cancer might be associated with a different outcome if compared with invasive ductal carcinoma with similar biological features and stages. Selected triple negative apocrine breast cancer can have an extremely good prognosis. Methods: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated between January 1998 and December 2016 at European Institute Oncology, Milan, we identified 24 patients with pT1-pT2, node-negative, triple negative subtype and Ki-67 20% who did not receive adjuvant chemotherapy. We compared the outcome of this cohort with a similar group of 48 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features (matching ratio 1:2). Results: The median age was 63 and 50 years in the apocrine and ductal group, respectively. The mean value of Ki-67 expression was 12% in the apocrine group and 14% in the ductal group. 83% of apocrine tumors had size less than 2 cm, compared with 71% of ductal tumors. After a median follow-up of 6.6 years no patients in the apocrine group experienced a breast cancer related event compared with 12 events (including 5 loco-regional recurrences, 3 distant recurrences e 4 contralateral tumors) in the ductal carcinoma group (Gray test p-value¼0.015). Conclusions: The outcome of selected apocrine triple negative breast cancer patients is excellent and possibly deserves a treatment de-escalation. Multicenter projects focusing on the possibility to avoid adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: G. Cancello: Honoraria (self): Pierre Fabre. E. Montagna: Honoraria (self): Pierre fabre; Honoraria (self): gentili. E. Munzone: Honoraria (institution), Advisory / Consultancy: Pierre Fabre; Honoraria (institution), Advisory / Consultancy: Genomic Health. S. Dellapasqua: Travel / Accommodation / Expenses: Roche. M.A. Colleoni: Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Advisory / Consultancy: OBI Pharma; Advisory / Consultancy: Puma Biotechnology; Advisory / Consultancy: Celldex; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.
256P
Novel blood based circulating tumour cell biomarker for breast cancer detection
C.-Y. Liu1, Y.-F. Tsai1, F.-M. Lin2, J.-C. Wu2, Y.-S. Lin1, T.-C. Chao1, K.-L. King1, P.-J. Lien1, J. Wang1, Y.-H. Lin1, Y.-C. Lai1, H.B. Hsieh2, A. Saklecha2, J.-M. Lai2, S.-E. Chang3, M. Javey3, D. Watson3, R. Mei2, L.-M. Tseng1 1 Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei, Taiwan, 2 R&D, CellMax Life, Sunnyvale, CA, USA, 3Clinical Affairs, CellMax Life, Sunnyvale, CA, USA
CI: 78.2%, 95.6%) sensitivity was 56.3% (95% CI: 43.3%, 68.6%) for the most common subtype ER/PRþHER2-, 36.4% (17.2%-59.3%) for HER2þ, 43.8% (19.8%- 70.1%) for TNBC, 46.5% (37.1%- 56.1%) overall. Sensitivity was 62.5% (35.4%- 84.8%) for late stage (Stage III/IV cancer) and 43.5% (33.2%- 54.2%) for early stage (Stage 0, I or II cancer) patients. In the subset of 41 individuals with an indeterminate classification of BIRADS 3 (likely benign) or BIRADS 4 (likely malignant) sensitivity was 90% and specificity was 47.6% (95% CI: 25.7%, 70.2%). Conclusions: In this initial study, CTC was a significant predictor of cancer. The CTC assay can easily be combined with cfDNA to enhance detection rates. Proof-of-concept data suggests potential for a rule out test to avoid unnecessary follow-up/biopsies in BIRADS 3/4 patients. Legal entity responsible for the study: CellMax Life. Funding: CellMax Life. Disclosure: F. Lin: Shareholder / Stockholder / Stock options: CellMax Life. J. Wu: Shareholder / Stockholder / Stock options: CellMax Life. H.B. Hsieh: Shareholder / Stockholder / Stock options: CellMax Life. S. Chang: Shareholder / Stockholder / Stock options: CellMax Life. M. Javey: Shareholder / Stockholder / Stock options: CellMax Life. D. Watson: Shareholder / Stockholder / Stock options: CellMax Life. R. Mei: Shareholder / Stockholder / Stock options: CellMax Life. All other authors have declared no conflicts of interest.
257P
C. Mazo1,2,3, S. Barron3, C. Mooney1, W.M. Gallagher3,4 UCD School of Computer Science, University College Dublin, Dublin, Ireland, 2CeADAR: Centre for Applied Data Analytics Research, Dublin, Ireland, 3OncoMark Limited, Dublin, Ireland, 4UCD School of Biomolecular & Biomedical Science, UCD Conway Institute, Dublin, Ireland 1
Background: Determining which early stage breast cancer patients should receive chemotherapy is an important clinical and economic issue. Chemotherapy has many adverse side effects, impacting on quality of life, along with significant economic consequences. Biomarkers that can predict patient response to chemotherapy can help avoid ineffective overtreatment. The aim of this work is to assess if the OncoMasTR (OM) signature can predict pathological complete response (pCR) to neo-adjuvant chemotherapy, and to compare its predictive value with EndoPredict (EP) and Oncotype DX (RS). Methods: Gene expression datasets derived from breast cancer patients that had pretreatment biopsies, received neo-adjuvant chemotherapy and an assessment of pCR were obtained from GEO (GSE16716, GSE20271, GSE25066, GSE32646, GSE34138, GSE41998, GSE22226). Patients with ER-positive, HER2-negative disease and pCR data were selected. OM, EP and RS numeric risk scores were approximated by applying the gene coefficients to the corresponding mean probe expression values. Association with pCR was estimated using logistic regression. Results: A total of 813 patients with 66 pCR events were included in the analysis. OM, EP and RS prognostic scores were moderately well correlated according to the Pearson’s correlation coefficient: OM vs EP (min¼0.44; mean¼0.67; max¼0.81), OM vs RS (min¼0.34; mean¼0.62; max¼0.79), and RS vs EP (min¼0.55; mean¼0.79; max¼0.89). Significant predictors of pCR with p-values of 0.0001 for all three signatures. Odds ratios for a 1 standard deviation increase in risk score, adjusted for cohort, were similar in magnitude and not significantly different: OM 1.66 (1.29 to 2.16), EP 1.76 (1.37 to 2.27), RS 1.84 (1.44 to 2.35). Conclusions: In this in silico analysis, OM, EP and RS prognostic scores were significantly predictive of pCR to neo-adjuvant chemotherapy in ER-positive, HER2-negative breast cancer. Optimal stratification for neo-adjuvant chemotherapy offers the opportunity for personalised care, improved therapy response rates, and reduced ineffective treatment and costs. Legal entity responsible for the study: University College Dublin. Funding: The EI and from the European Union’s Horizon 2020 research and innovation programme under the Marie Slodowska-Curie grant agreement No. 713654. Disclosure: The author has declared no conflicts of interest.
258P Background: There is an unmet need for a blood test to detect breast cancer in women with dense breast tissue or clinically aggressive subtypes that may be missed by mammograms. Cell-free DNA in blood has shown 15-58% sensitivity for breast cancer. We evaluated the performance of a circulating tumor cell (CTC) assay as a complimentary biomarker for detecting breast cancer in an Asian population, which has high incidence of dense breast tissue. Methods: A single-center, IRB-approved, prospective and blinded clinical study was conducted on 114 Taiwanese females with biopsy-confirmed breast cancer, and 50 healthy controls confirmed by ultrasound or mammogram. Four milliliter of blood was collected prior to imaging and processed using the CellMax biomimetic platform (CMx) which enumerates CTCs utilizing selection criteria based on a set of markers (cytokeratin 18, mammaglobin, CD45), cell morphometry (size, N/C ratio) and nucleus morphology. Logistic regression models for CMx CTC counts and patient age were used to assess the classification performance of the CMx test. Results: Of the 114 cancer (80% were stage 02), the subtypes were confirmed for 102 (62% ER/PRþ HER2-, 22% HER2þ, 16% TNBC). CTC count was a significant predictor of cancer status (Likelihood Ratio P-value ¼ 0.0001). At 90% specificity (exact 95%
v86 | Breast Cancer, Early Stage
Multi-gene prognostic signatures and prediction of pathological complete response of ER-Positive HER2-negative breast cancer patients to neo-adjuvant chemotherapy
Impact of menopause status on breast cancer outcomes and amenorrhea incidence during adjuvant tailored dose dense chemotherapy
A. Papakonstantinou1, A. Matikas1, M. Hellstro¨m2, H. Johansson2, G. Steger3, R. Greil4, S. Loibl5, M. Gnant6, V. Moebus7, M. Untch8, T. Foukakis1, J. Bergh1 1 Department of Oncology-Pathology, Karolinska Institutet - Bioclinicum, Stockholm, Sweden, 2CKC, Karolinska University Hospital-Solna, Stockholm, Sweden, 3Medical Oncology, Austria and Gaston H. Glock Research Center, Medical University, Vienna, Austria,4Medical Department, Paracelsus Medical University, Salzburg, Austria, 5German Breast Group, Neu-Isenburg, Germany, 6Department of Surgery, Medical University of Vienna, Vienna, Austria, 7Department of Gynecology and Obstetrics, Klinikum Frankfurt Ho¨chst, Academic Hospital Goethe University, Frankfurt, Germany, 8Clinic for Gynecology, Gynecologic Oncology and Obstetrics, Helios Klinikum Berlin Buch, Berlin, Germany Background: Adjuvant dose-dense chemotherapy improves breast cancer (BC) outcomes compared to standard chemotherapy, with no increase in chemotherapy-
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.081/5576387 by guest on 26 October 2019
G. Cancello1, E. Montagna1, E. Pagan2, V. Bagnardi2, E. Munzone1, S. Dellapasqua1, M. Iorfida1, M. Mazza1, A.P. De Maio1, G. Viale3, G. Mazzarol3, P. Veronesi4, V. Galimberti1, G. Santomauro1, M.A. Colleoni5 1 Division Of Medical Senology, Istituto Europeo di Oncologia, Milan, Italy, 2Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy, 3 Division of Pathology, Istituto Europeo di Oncologia, Milan, Italy, 4Senology, Istituto Europeo di Oncologia, Milan, Italy, 5International Breast Cancer Study Group, Division of Medical Senology, Istituto Europeo di Oncologia, Milan, Italy
Annals of Oncology