- Email: [email protected]
The value of genetic counselling in breast cancer genetic testing and clinical management
abstracts
235P
Study on the socioeconomic and clinical factors affecting the proportion of breast conserving surgery in Chinese women breast cancer
J. Zhang Breast Cancer Department, Tianjin Cancer Hospital, Tianjin, China Background: This study intends to investigate the socioeconomic and clinical factors affecting the proportion of breast conserving surgery (BCS) in China. Methods: A total of 51237 breast cancer patients were treated in Tianjin Medical University cancer institute &Hospital from January 2005 to January 2018. In order to improve the success rate of BCS, we choose 5660 patients prepared to be treated by BCS to make analysis of independent factors affecting initial positive margins. Finally, we analyzed the survival trend of breast cancer patients after increasing the proportion of BCS by comparing the locoregional free survival (LRRFS), distant metastasis free survival (DMFS), overall survival (OS) of breast cancer patients. Results: Multivariate analysis showed the distance from nipple (P ¼ 0.030), tumor distribution along the duct (OR¼2.599,P<0.001), pathological subtype (P < 0.001) and lymph node metastasis (OR ¼ 0.299, P < 0.001), no preoperative MRI examination (OR ¼ 1.291,p¼0.001)were independent predictors of positive resection margins. Multivariate analysis revealed that tumor size(OR¼0.706,P<0.001), non-mass enhancement (NME)(OR¼4.443,P¼0.001), malignant enhancement surrounding tumor (OR¼1.647, P<0.001) were independent predictors of positive resection margins. The survival analysis of breast cancer patients after increasing the proportion of BCS revealed that the 5-LRRFS of 2005-2010 and 2011-2013 were 97.2%,98.4%, respectively. The 5-DMFS of 2005-2010 and 2011-2013 were 94.1%, 95.2 %, respectively, without significant difference. The OS of 2005-2010 and 2011-2013 were 96.4%, 97.9% respectively. Conclusions: In China,we should gradually reduce the influence of socioeconomic factors on the proportion of breast conserving surgery in the future. Preoperative MRI should be encouraged in patients preparing for BCS. Clinicopathological characteristics and MRI findings are significantly associated with a positive resection margin in breast cancer patients. Legal entity responsible for the study: The author. Funding: The National Natural Science Foundation of China (81672623). Disclosure: The author has declared no conflicts of interest.
v78 | Breast Cancer, Early Stage
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Clinical decision making and multidisciplinary team meetings (MDMs) in early breast cancer. Is the agreement between planned and applied therapeutic program?
M. Giavarra1,2, E. Bertoli1,2, V. Buoro1,2, D. Zara1,2, G. Targato1,2, L. Palmero1,2, M.G. Vitale1,2, G. Pelizzari3,4, D. Basile3,4, L. Gerratana3,4, M. Bonotto5, C. Andreetta5, M. Cinausero5, G. Pascoletti5, E. Poletto5, S. Russo5, F. Puglisi3,4, G. Fasola5, M. Mansutti5, A.M. Minisini5 1 Oncologia Medica, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italia, 2 Dipartimento di Medicina (DAME), Universit a degli Studi di Udine, Udine, Italy, 3 Dipartimento di Medicina (DAME), Universit a di Udine, Udine, Italia, 4Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, 5 Italy, Oncologia Medica, Azienda Sanitaria Universitaria Integrata di Udine - Ospedale Santa Maria della Misericordia, Udine, Italy Background: Cancer multidisciplinary team meetings (MDMs) are commonly acknowledged as a good clinical practice. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early breast cancer (EBC). In this setting, the purpose of the study was to define whether there was agreement between the planned program (i.e. MDMs-based decision) and that actually applied (i.e. actual therapeutic choice, ATC). In addition, the study explored factors associated with discordance. Methods: We conducted a monocentric retrospective study of a consecutive series of 291 pts with new diagnosis of EBC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. Results: Median age was 62 years (range 27-88 years). Among invasive EBC patients, the most frequent phenotype was luminal-A (38%), followed by luminal-B (33%), HER2positive (12%) and triple negative (5%). Thirty-four pts (12%) had diagnosis of in situ carcinoma (DCIS). Median time from MDMs discussion to first oncological examination was two weeks. Rate of discordance between MDMs-based decision and final choice, during face to face consultation with the oncologist, was 15.8% (46/291). Among cases with discordance, 19 pts (41.3%) had age > 70 years; 8 pts (17%) had a diagnosis of DCIS, 13 pts (28%) luminal-B carcinoma, 12 pts (26%) luminal-A, 9 pts (20%) HER2-positive and 4 pts (9%) triple negative EBC. The most frequent reason for changing the MDMs-based program was clinical decision by the oncologist at the first evaluation (87%). Follow-up was preferred to the chemotherapy proposed within the MDMs by 15% of pts, and to the endocrine therapy in 39% cases (among these, 44.5% had diagnosis of DCIS). In our study 16/46 pts (35%) had a therapeutic change from chemotherapy to endocrine therapy: among these pts, 7/16 had a luminal-B and 6/16 had a HER2-positive disease. Further analysis aiming at evaluating variables which could predict discordance between MDMs proposal and face to face oncological consultation are ongoing. Conclusions: The results of our study could be useful for enhance the role of MTD and identify unmet needs in decision making process in EBC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
237P
The value of genetic counselling in breast cancer genetic testing and clinical management
V. Kiesel1, G. Wishart2 1 Genetics, Genehealth UK, Cambridge, UK, 2Surgery, Check4Cancer, Cambridge, UK Background: Multiple national1 and international2 guidelines recommend that genetic testing is provided by genetic experts in the context of genetic counselling. However, there has been little research performed assessing the utility of genetic counselling. This study was performed to determine the value of genetic counselling for individuals undergoing breast cancer genetic testing. Methods: GeneHealth UK clinical records for patients seen between the 1st January 2018 and 30th June 2018 for breast cancer were reviewed to determine what was discussed during the consultations. Data was collated in four categories: a) appropriateness of genetic testing, b) psychological support, c) implications for relatives d) management guidance. Results: Of a total of 130 patients, 74% (96) had breast cancer, and 26% (34) had a family history. 10% of tested patients had a pathogenic genetic variant. 98% of patients had at least one discussion in the assessed areas; 16% had two, 21% had three and 52% had four or more. Genetic counselling helped 15% of patients decide not to proceed with genetic testing: either because a relative would be more appropriate to test (5%), the patient had a low risk of a BRCA mutation (3%) or for psychological reasons (7%). Psychological support was provided to 15% of patients including the provision of support resources in 12% and referral for counselling in 2% of cases. Genetic counsellors assess the whole family and were therefore able to provide screening recommendations for relatives in 62% of cases and assess risk of other familial conditions in 2% of families. Of importance external referrals were made in 6% of patients. Conclusions: Genetic counselling provides significant psychosocial and practical benefits in the provision of breast cancer genetics: including advice for the whole family, ensuring genetic testing is appropriate and referral to appropriate external healthcare agencies. 1 NICE Guidance 2 NCCN Guidelines. Legal entity responsible for the study: The authors. Funding: Has not received any funding.
Volume 30 | Supplement 5 | October 2019
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Methods: Twenty breast cancer female survivors were recruited to a single-arm clinical trial consisting of sequential 16 weeks (wk) of control phase (CP) and 16 wk intervention phase (IP). Four evaluations were carried out: M1 (8 wk on CP), M2 (immediately previous IP), M3 (8 wk CP) and M4 (16 wk IP). The IP consisted of 3 sessions per week of combined aerobic and strength exercise (60min) at moderate to vigorous exercise (65-85% of maximum heart rate or 6-8 points on OMNI scale). The primary endpoint was QoL, which was evaluated by EORTC QLQ-C30 questionnaire. Secondary endpoints included handgrip strength and sit-to-stand (STS) test. Results: Of the 20 recruited women, 19 initiated and 15 concluded the program, with a mean compliance to the exercise intervention of 63.6%. The median age was 59 years old (39-72). All but 3 were diagnosed with invasive carcinoma. After surgery, 13 (62%) underwent radiotherapy, 15 (71%) chemotherapy and 18 (86%) were under hormonotherapy. During the control phase, no significant differences were observed in the efficacy variables. There was no changes over time for any domain of QoL, except for physical functioning scale (p ¼ 0.038), where it was observed a trend to increase between M2 and M3 (77.3614.0 to 85.3610.1, p ¼ 0.051). A significant increase in handgrip strength of non-operated (22.263.9 to 25.665.3 kg.f, p ¼ 0.004) and operated limb (22.664.7 to 26.966.6 kg.f, p ¼ 0.001) was shown after exercise training. Similar results were also observed for STS test [12 (11-13.5) to 17 (13-21) repetitions, p ¼ 0.002]. Conclusions: An exercise program appears to be beneficial for QoL, particularly in the physical functioning of breast cancer survivors. Moreover, it seems to have an important role on strength levels. Legal entity responsible for the study: Associac¸~ao de Investigac¸~ao e Cuidados de Suporte em Oncologia. Funding: Liga Portuguesa Contra o Cancro. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology Disclosure: V. Kiesel: Shareholder / Stockholder / Stock options: Genehealth UK. G. Wishart: Shareholder / Stockholder / Stock options: Check4Cancer.
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Elderly patients in the Japanese breast cancer registry
Background: Aim: To clarify the clinicopathological characters and treatments and prognosis in elderly breast cancer patients using the Japanese Breast Cancer Registry (JBCR) system. Methods: We reviewed data from JBCR, which is the nation-wide registry of newly diagnosed and operated primary breast cancer patients in Japan. To clarify its characteristics, we compared elderly patients aged 75 and over (elderly) with aged from 65 to 74 (young-old; y-o) and that from 55 to 64 (post-menopausal; p-m), respectively. Results: In total 132,240 cases diagnosed between 2004 and 2011 were reviewed (elderly; n ¼ 27,385, y-o; n ¼ 43,839, p-m; n ¼ 61,016). In histology, the proportion of mucinous carcinoma and apocrine carcinoma were higher in elderly (6.1%, 1.8%, y-o; 3.5%, 1.7%, p-m; 1.8%, 1.3%, respectively). Patients with clinical stage II and III were more frequent in elderly (45.1%, y-o; 39.0%, p-m; 39.8%). ER -positive rate was higher (76.8%, y-o; 76.3%, p-m; 72.7%) and HER2-positive rate was lower in elderly (10.5%, y-o; 12.8%, p-m; 18.6%, p < 0.001). As for surgery, the rate of breast conserving surgery (BCS) was lower in elderly (46.4%, y-o; 55.0%, p-m; 59.6%), and the rate of no surgery for axilla was higher in elderly (18.4%, y-o; 5.9%, p-m; 4.8%, p < 0.001). Irradiation after BCS was performed only in 41.3% of elderly patients, whereas y-o and p-m were 75.9%, 83.0%, respectively. Adjuvant chemotherapy was performed only in 10.8% of elderly patients, y-o and p-m were 31.8%, 46.2%, respectively. Half of elderly patients (49.8%) who underwent chemotherapy were given CMF or oral 5FU. As for hormone therapy, Tamoxifen was used more frequently in elderly (18.1%, y-o; 10.6%, p-m; 9.7%). The 5 years-survival analysis is shown in Table.
Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cergentis; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Adienne; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Genentch; Research grant / Funding (institution): Tesaro. M. Kok: Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.
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Table: 238P Age
⭌75
65-74
55-64
Distant disease-free survival (%) Overall survival (%) Breast cancer-specific survival (BCSS) (%) Other disease death (%)
93.1 84.3 94.2 48.0
94.3 93.7 96.7 35.8
93.1 94.4 95.9 20.6
Conclusions: Elderly patients suffered from more advanced disease at the time of diagnosis. Irradiation after BCS and primary systemic chemotherapy was more frequently omitted in the elderly patients. Overall, BCSS was similar among ages, but the rate of other causes of death was higher in elderly patients. Legal entity responsible for the study: The authors. Funding: Japanese Breast Cancer Society. Disclosure: All authors have declared no conflicts of interest.
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Tumour-infiltrating lymphocytes and BRCA-like status in stage III breast cancer patients treated with intensified carboplatin-based chemotherapy
L. De Boo1, A. Cimino-Mathews2, Y. Lubeck1, A. Daletzakis1, M. Opdam1, J. Sanders1, E. Hooijberg3, A.G.J. van Rossum1, Z. Loncova4, D. Rieder4, Z. Trajanoski4, M. Vollebergh5, M. Sobral-Leite1, K. Van de Vijver6, A. Broeks7, R. van der Wiel1, H. van Tinteren1, S.C. Linn5, H. Horlings1, M. Kok8 1 Molecular Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands, 2Pathology and Oncology, The Johns Hopkins Hospital, Baltimore, MD, USA, 3Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands, 4Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria, 5Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands, 6Department of Pathology, Ghent University Hospital, Gent, Belgium, 7Department of Pathology, Netherlands Cancer Institute/ Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands, 8Department of Medical Oncology and Division of Molecular Oncology & Immunology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands
Unravelling the biological characteristics of MammaPrint extreme risk subgroups
R. Bhaskaran1, C. Griffioen1, D. Wehkamp2, L. Mittempergher1, A.M. Glas3 Research & Development, Agendia Inc., Amsterdam, Netherlands, 2Scientific Computing, Agendia Inc., Amsterdam, Netherlands, 3Product Development, Agendia Inc., Amsterdam, Netherlands
1
R (MP) is a 70-gene based prognostic assay that stratifies Background: MammaPrintV early-stage breast cancer patients into low and high-risk of relapse. Recently, further stratification of the 70-gene risk results identified extreme low and high-risk subgroups with specific clinical outcomes (Delahaye et al. 2017) and treatment response characteristics (Wolf et al. 2017). However, the biological profiles of these extreme MP subgroups are not fully investigated. In this study, we aim to gain more insight into their biological significance using differentially expression genes (DEGs) analysis. Methods: We selected 400 samples from the whole MP range and defined 4 subgroups (Ultra high [UH], High risk [HR], Low risk [LR], Ultra low [UL]), for which FFPE microarray full-transcriptome data were available at Agendia. DEGs analysis was performed with limma and subsequent pathway analysis with Enrichr and GOrilla. Results: Two separate comparative analyses were carried out to unravel biological processes associated with extreme risk subgroups: UL vs. LR and UH vs. HR. We found 101 DEGs (logFC > ¼0.485 & FDR <0.05) between UL and LR subgroups and 1714 DEGs between UH and HR subgroups. Based on the pathway analysis, our results showed that the UL subgroup was more homogeneous, with enrichment in pathways reflecting low proliferative and metastatic features. This is in line with the favorable long-term outcome characteristic of the UL group. Conversely UH exhibited higher heterogeneity, with the enrichment of more diverse pathways including immune response, cell cycle and proliferation, that could be associated with genomic instability. This would support the recent finding of UH samples being more sensitive to veliparib/ carboplatin combination therapy compared to HR samples (Wolf et al. 2017)). Furthermore, clustering approach demonstrated UH and other subgroups as two distinct clusters. Conclusions: Our preliminary findings give additional insights into the biological processes associated with extreme MP groups, which might open new avenues for therapeutic intervention in breast cancer. Legal entity responsible for the study: Agendia Inc. Funding: Agendia Inc. Disclosure: R. Bhaskaran: Full / Part-time employment: Agendia Inc. C. Griffioen: Full / Part-time
employment: Agendia Inc. D. Wehkamp: Full / Part-time employment: Agendia Inc. L. Mittempergher: Full / Part-time employment: Agendia Inc. A.M. Glas: Full / Part-time employment: Agendia Inc.
Background: The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz240 | v79
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M. Sawaki1, A. Yamada2, H. Kumamaru3, H. Miyata3, C. Shimizu4, M. Miyashita5, N. Honma6, N. Taira7, S. Saji8 1 Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, 2Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan, 3Healthcare Quality Assessment, Graduate School of Medicine, Tokyo University, Tokyo, Japan, 4 Breast Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan, 5Nursing Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan, 6Pathology, Toho University School of Medicine, Tokyo, Japan, 7Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan, 8Medical Oncology, Fukushima Medical University, Fukushima, Japan
in the context of BRCA1/2-like phenotypes and their association with outcome and benefit of intensified platinum-based chemotherapy. Methods: Patients in this study participated in a randomized controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracyclinebased chemotherapy carried out between 1993-1999 in stage III BC. Stromal TILs were scored according to International guidelines in these HER2-negative tumours. BRCAprofiles were determined using array-based Comparative Genomic Hybridization (aCGH) data. Results: TIL levels were evaluated in 248 stage III breast tumours. High TILs are associated with TNBC. Tumours were classified as non-BRCA-like (n ¼ 167), BRCA1-like (n ¼ 30), BRCA2-like (n ¼ 39) or BRCA1/2-like (n ¼ 12). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% vs 10%, respectively, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like (median TILs of 20% vs 10%, respectively, p < 0.001) and non-BRCAlike tumours (median TILs of 10%, p < 0.001). These correlations remained significant within the ER-positive subgroup. Within TNBC, TIL levels were not higher in BRCAlike compared to non-BRCA-like tumours (median TILs of 30% vs 25%, respectively, p ¼ 0.96). In this stage III BC cohort, high TIL level was associated with favourable outcome regarding recurrence-free and overall survival (TILs per 10% increment, HR 0.82, 95% CI 0.71-0.94, p ¼ 0.01, respectively HR 0.80, 95% CI 0.68-0.94, p ¼ 0.01). There was no significant interaction between TIL levels and benefit of intensified platinum-based chemotherapy. Conclusions: In this high-risk breast cancer cohort, high TILs were associated with TNBC and BRCA1-like status. Within the ER-positive subgroup, TIL levels were higher in BRCA1-like compared to non-BRCA-like tumours, but this was not seen within the TNBC subgroup. When adjusted for clinical characteristics, TIL levels were significantly associated with a more favourable outcome in stage III BC patients. Legal entity responsible for the study: The authors. Funding: Dutch Cancer Society. Disclosure: A. Cimino-Mathews: Research grant / Funding (self): BMS. S.C. Linn: Advisory /
235P
Study on the socioeconomic and clinical factors affecting the proportion of breast conserving surgery in Chinese women breast cancer
J. Zhang Breast Cancer Department, Tianjin Cancer Hospital, Tianjin, China Background: This study intends to investigate the socioeconomic and clinical factors affecting the proportion of breast conserving surgery (BCS) in China. Methods: A total of 51237 breast cancer patients were treated in Tianjin Medical University cancer institute &Hospital from January 2005 to January 2018. In order to improve the success rate of BCS, we choose 5660 patients prepared to be treated by BCS to make analysis of independent factors affecting initial positive margins. Finally, we analyzed the survival trend of breast cancer patients after increasing the proportion of BCS by comparing the locoregional free survival (LRRFS), distant metastasis free survival (DMFS), overall survival (OS) of breast cancer patients. Results: Multivariate analysis showed the distance from nipple (P ¼ 0.030), tumor distribution along the duct (OR¼2.599,P<0.001), pathological subtype (P < 0.001) and lymph node metastasis (OR ¼ 0.299, P < 0.001), no preoperative MRI examination (OR ¼ 1.291,p¼0.001)were independent predictors of positive resection margins. Multivariate analysis revealed that tumor size(OR¼0.706,P<0.001), non-mass enhancement (NME)(OR¼4.443,P¼0.001), malignant enhancement surrounding tumor (OR¼1.647, P<0.001) were independent predictors of positive resection margins. The survival analysis of breast cancer patients after increasing the proportion of BCS revealed that the 5-LRRFS of 2005-2010 and 2011-2013 were 97.2%,98.4%, respectively. The 5-DMFS of 2005-2010 and 2011-2013 were 94.1%, 95.2 %, respectively, without significant difference. The OS of 2005-2010 and 2011-2013 were 96.4%, 97.9% respectively. Conclusions: In China,we should gradually reduce the influence of socioeconomic factors on the proportion of breast conserving surgery in the future. Preoperative MRI should be encouraged in patients preparing for BCS. Clinicopathological characteristics and MRI findings are significantly associated with a positive resection margin in breast cancer patients. Legal entity responsible for the study: The author. Funding: The National Natural Science Foundation of China (81672623). Disclosure: The author has declared no conflicts of interest.
v78 | Breast Cancer, Early Stage
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Clinical decision making and multidisciplinary team meetings (MDMs) in early breast cancer. Is the agreement between planned and applied therapeutic program?
M. Giavarra1,2, E. Bertoli1,2, V. Buoro1,2, D. Zara1,2, G. Targato1,2, L. Palmero1,2, M.G. Vitale1,2, G. Pelizzari3,4, D. Basile3,4, L. Gerratana3,4, M. Bonotto5, C. Andreetta5, M. Cinausero5, G. Pascoletti5, E. Poletto5, S. Russo5, F. Puglisi3,4, G. Fasola5, M. Mansutti5, A.M. Minisini5 1 Oncologia Medica, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italia, 2 Dipartimento di Medicina (DAME), Universit a degli Studi di Udine, Udine, Italy, 3 Dipartimento di Medicina (DAME), Universit a di Udine, Udine, Italia, 4Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, 5 Italy, Oncologia Medica, Azienda Sanitaria Universitaria Integrata di Udine - Ospedale Santa Maria della Misericordia, Udine, Italy Background: Cancer multidisciplinary team meetings (MDMs) are commonly acknowledged as a good clinical practice. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early breast cancer (EBC). In this setting, the purpose of the study was to define whether there was agreement between the planned program (i.e. MDMs-based decision) and that actually applied (i.e. actual therapeutic choice, ATC). In addition, the study explored factors associated with discordance. Methods: We conducted a monocentric retrospective study of a consecutive series of 291 pts with new diagnosis of EBC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. Results: Median age was 62 years (range 27-88 years). Among invasive EBC patients, the most frequent phenotype was luminal-A (38%), followed by luminal-B (33%), HER2positive (12%) and triple negative (5%). Thirty-four pts (12%) had diagnosis of in situ carcinoma (DCIS). Median time from MDMs discussion to first oncological examination was two weeks. Rate of discordance between MDMs-based decision and final choice, during face to face consultation with the oncologist, was 15.8% (46/291). Among cases with discordance, 19 pts (41.3%) had age > 70 years; 8 pts (17%) had a diagnosis of DCIS, 13 pts (28%) luminal-B carcinoma, 12 pts (26%) luminal-A, 9 pts (20%) HER2-positive and 4 pts (9%) triple negative EBC. The most frequent reason for changing the MDMs-based program was clinical decision by the oncologist at the first evaluation (87%). Follow-up was preferred to the chemotherapy proposed within the MDMs by 15% of pts, and to the endocrine therapy in 39% cases (among these, 44.5% had diagnosis of DCIS). In our study 16/46 pts (35%) had a therapeutic change from chemotherapy to endocrine therapy: among these pts, 7/16 had a luminal-B and 6/16 had a HER2-positive disease. Further analysis aiming at evaluating variables which could predict discordance between MDMs proposal and face to face oncological consultation are ongoing. Conclusions: The results of our study could be useful for enhance the role of MTD and identify unmet needs in decision making process in EBC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
237P
The value of genetic counselling in breast cancer genetic testing and clinical management
V. Kiesel1, G. Wishart2 1 Genetics, Genehealth UK, Cambridge, UK, 2Surgery, Check4Cancer, Cambridge, UK Background: Multiple national1 and international2 guidelines recommend that genetic testing is provided by genetic experts in the context of genetic counselling. However, there has been little research performed assessing the utility of genetic counselling. This study was performed to determine the value of genetic counselling for individuals undergoing breast cancer genetic testing. Methods: GeneHealth UK clinical records for patients seen between the 1st January 2018 and 30th June 2018 for breast cancer were reviewed to determine what was discussed during the consultations. Data was collated in four categories: a) appropriateness of genetic testing, b) psychological support, c) implications for relatives d) management guidance. Results: Of a total of 130 patients, 74% (96) had breast cancer, and 26% (34) had a family history. 10% of tested patients had a pathogenic genetic variant. 98% of patients had at least one discussion in the assessed areas; 16% had two, 21% had three and 52% had four or more. Genetic counselling helped 15% of patients decide not to proceed with genetic testing: either because a relative would be more appropriate to test (5%), the patient had a low risk of a BRCA mutation (3%) or for psychological reasons (7%). Psychological support was provided to 15% of patients including the provision of support resources in 12% and referral for counselling in 2% of cases. Genetic counsellors assess the whole family and were therefore able to provide screening recommendations for relatives in 62% of cases and assess risk of other familial conditions in 2% of families. Of importance external referrals were made in 6% of patients. Conclusions: Genetic counselling provides significant psychosocial and practical benefits in the provision of breast cancer genetics: including advice for the whole family, ensuring genetic testing is appropriate and referral to appropriate external healthcare agencies. 1 NICE Guidance 2 NCCN Guidelines. Legal entity responsible for the study: The authors. Funding: Has not received any funding.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.061/5576220 by guest on 24 October 2019
Methods: Twenty breast cancer female survivors were recruited to a single-arm clinical trial consisting of sequential 16 weeks (wk) of control phase (CP) and 16 wk intervention phase (IP). Four evaluations were carried out: M1 (8 wk on CP), M2 (immediately previous IP), M3 (8 wk CP) and M4 (16 wk IP). The IP consisted of 3 sessions per week of combined aerobic and strength exercise (60min) at moderate to vigorous exercise (65-85% of maximum heart rate or 6-8 points on OMNI scale). The primary endpoint was QoL, which was evaluated by EORTC QLQ-C30 questionnaire. Secondary endpoints included handgrip strength and sit-to-stand (STS) test. Results: Of the 20 recruited women, 19 initiated and 15 concluded the program, with a mean compliance to the exercise intervention of 63.6%. The median age was 59 years old (39-72). All but 3 were diagnosed with invasive carcinoma. After surgery, 13 (62%) underwent radiotherapy, 15 (71%) chemotherapy and 18 (86%) were under hormonotherapy. During the control phase, no significant differences were observed in the efficacy variables. There was no changes over time for any domain of QoL, except for physical functioning scale (p ¼ 0.038), where it was observed a trend to increase between M2 and M3 (77.3614.0 to 85.3610.1, p ¼ 0.051). A significant increase in handgrip strength of non-operated (22.263.9 to 25.665.3 kg.f, p ¼ 0.004) and operated limb (22.664.7 to 26.966.6 kg.f, p ¼ 0.001) was shown after exercise training. Similar results were also observed for STS test [12 (11-13.5) to 17 (13-21) repetitions, p ¼ 0.002]. Conclusions: An exercise program appears to be beneficial for QoL, particularly in the physical functioning of breast cancer survivors. Moreover, it seems to have an important role on strength levels. Legal entity responsible for the study: Associac¸~ao de Investigac¸~ao e Cuidados de Suporte em Oncologia. Funding: Liga Portuguesa Contra o Cancro. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology Disclosure: V. Kiesel: Shareholder / Stockholder / Stock options: Genehealth UK. G. Wishart: Shareholder / Stockholder / Stock options: Check4Cancer.
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Elderly patients in the Japanese breast cancer registry
Background: Aim: To clarify the clinicopathological characters and treatments and prognosis in elderly breast cancer patients using the Japanese Breast Cancer Registry (JBCR) system. Methods: We reviewed data from JBCR, which is the nation-wide registry of newly diagnosed and operated primary breast cancer patients in Japan. To clarify its characteristics, we compared elderly patients aged 75 and over (elderly) with aged from 65 to 74 (young-old; y-o) and that from 55 to 64 (post-menopausal; p-m), respectively. Results: In total 132,240 cases diagnosed between 2004 and 2011 were reviewed (elderly; n ¼ 27,385, y-o; n ¼ 43,839, p-m; n ¼ 61,016). In histology, the proportion of mucinous carcinoma and apocrine carcinoma were higher in elderly (6.1%, 1.8%, y-o; 3.5%, 1.7%, p-m; 1.8%, 1.3%, respectively). Patients with clinical stage II and III were more frequent in elderly (45.1%, y-o; 39.0%, p-m; 39.8%). ER -positive rate was higher (76.8%, y-o; 76.3%, p-m; 72.7%) and HER2-positive rate was lower in elderly (10.5%, y-o; 12.8%, p-m; 18.6%, p < 0.001). As for surgery, the rate of breast conserving surgery (BCS) was lower in elderly (46.4%, y-o; 55.0%, p-m; 59.6%), and the rate of no surgery for axilla was higher in elderly (18.4%, y-o; 5.9%, p-m; 4.8%, p < 0.001). Irradiation after BCS was performed only in 41.3% of elderly patients, whereas y-o and p-m were 75.9%, 83.0%, respectively. Adjuvant chemotherapy was performed only in 10.8% of elderly patients, y-o and p-m were 31.8%, 46.2%, respectively. Half of elderly patients (49.8%) who underwent chemotherapy were given CMF or oral 5FU. As for hormone therapy, Tamoxifen was used more frequently in elderly (18.1%, y-o; 10.6%, p-m; 9.7%). The 5 years-survival analysis is shown in Table.
Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cergentis; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Adienne; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Genentch; Research grant / Funding (institution): Tesaro. M. Kok: Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.
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Table: 238P Age
⭌75
65-74
55-64
Distant disease-free survival (%) Overall survival (%) Breast cancer-specific survival (BCSS) (%) Other disease death (%)
93.1 84.3 94.2 48.0
94.3 93.7 96.7 35.8
93.1 94.4 95.9 20.6
Conclusions: Elderly patients suffered from more advanced disease at the time of diagnosis. Irradiation after BCS and primary systemic chemotherapy was more frequently omitted in the elderly patients. Overall, BCSS was similar among ages, but the rate of other causes of death was higher in elderly patients. Legal entity responsible for the study: The authors. Funding: Japanese Breast Cancer Society. Disclosure: All authors have declared no conflicts of interest.
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Tumour-infiltrating lymphocytes and BRCA-like status in stage III breast cancer patients treated with intensified carboplatin-based chemotherapy
L. De Boo1, A. Cimino-Mathews2, Y. Lubeck1, A. Daletzakis1, M. Opdam1, J. Sanders1, E. Hooijberg3, A.G.J. van Rossum1, Z. Loncova4, D. Rieder4, Z. Trajanoski4, M. Vollebergh5, M. Sobral-Leite1, K. Van de Vijver6, A. Broeks7, R. van der Wiel1, H. van Tinteren1, S.C. Linn5, H. Horlings1, M. Kok8 1 Molecular Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands, 2Pathology and Oncology, The Johns Hopkins Hospital, Baltimore, MD, USA, 3Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands, 4Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria, 5Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands, 6Department of Pathology, Ghent University Hospital, Gent, Belgium, 7Department of Pathology, Netherlands Cancer Institute/ Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands, 8Department of Medical Oncology and Division of Molecular Oncology & Immunology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands
Unravelling the biological characteristics of MammaPrint extreme risk subgroups
R. Bhaskaran1, C. Griffioen1, D. Wehkamp2, L. Mittempergher1, A.M. Glas3 Research & Development, Agendia Inc., Amsterdam, Netherlands, 2Scientific Computing, Agendia Inc., Amsterdam, Netherlands, 3Product Development, Agendia Inc., Amsterdam, Netherlands
1
R (MP) is a 70-gene based prognostic assay that stratifies Background: MammaPrintV early-stage breast cancer patients into low and high-risk of relapse. Recently, further stratification of the 70-gene risk results identified extreme low and high-risk subgroups with specific clinical outcomes (Delahaye et al. 2017) and treatment response characteristics (Wolf et al. 2017). However, the biological profiles of these extreme MP subgroups are not fully investigated. In this study, we aim to gain more insight into their biological significance using differentially expression genes (DEGs) analysis. Methods: We selected 400 samples from the whole MP range and defined 4 subgroups (Ultra high [UH], High risk [HR], Low risk [LR], Ultra low [UL]), for which FFPE microarray full-transcriptome data were available at Agendia. DEGs analysis was performed with limma and subsequent pathway analysis with Enrichr and GOrilla. Results: Two separate comparative analyses were carried out to unravel biological processes associated with extreme risk subgroups: UL vs. LR and UH vs. HR. We found 101 DEGs (logFC > ¼0.485 & FDR <0.05) between UL and LR subgroups and 1714 DEGs between UH and HR subgroups. Based on the pathway analysis, our results showed that the UL subgroup was more homogeneous, with enrichment in pathways reflecting low proliferative and metastatic features. This is in line with the favorable long-term outcome characteristic of the UL group. Conversely UH exhibited higher heterogeneity, with the enrichment of more diverse pathways including immune response, cell cycle and proliferation, that could be associated with genomic instability. This would support the recent finding of UH samples being more sensitive to veliparib/ carboplatin combination therapy compared to HR samples (Wolf et al. 2017)). Furthermore, clustering approach demonstrated UH and other subgroups as two distinct clusters. Conclusions: Our preliminary findings give additional insights into the biological processes associated with extreme MP groups, which might open new avenues for therapeutic intervention in breast cancer. Legal entity responsible for the study: Agendia Inc. Funding: Agendia Inc. Disclosure: R. Bhaskaran: Full / Part-time employment: Agendia Inc. C. Griffioen: Full / Part-time
employment: Agendia Inc. D. Wehkamp: Full / Part-time employment: Agendia Inc. L. Mittempergher: Full / Part-time employment: Agendia Inc. A.M. Glas: Full / Part-time employment: Agendia Inc.
Background: The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz240 | v79
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M. Sawaki1, A. Yamada2, H. Kumamaru3, H. Miyata3, C. Shimizu4, M. Miyashita5, N. Honma6, N. Taira7, S. Saji8 1 Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, 2Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan, 3Healthcare Quality Assessment, Graduate School of Medicine, Tokyo University, Tokyo, Japan, 4 Breast Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan, 5Nursing Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan, 6Pathology, Toho University School of Medicine, Tokyo, Japan, 7Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan, 8Medical Oncology, Fukushima Medical University, Fukushima, Japan
in the context of BRCA1/2-like phenotypes and their association with outcome and benefit of intensified platinum-based chemotherapy. Methods: Patients in this study participated in a randomized controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracyclinebased chemotherapy carried out between 1993-1999 in stage III BC. Stromal TILs were scored according to International guidelines in these HER2-negative tumours. BRCAprofiles were determined using array-based Comparative Genomic Hybridization (aCGH) data. Results: TIL levels were evaluated in 248 stage III breast tumours. High TILs are associated with TNBC. Tumours were classified as non-BRCA-like (n ¼ 167), BRCA1-like (n ¼ 30), BRCA2-like (n ¼ 39) or BRCA1/2-like (n ¼ 12). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% vs 10%, respectively, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like (median TILs of 20% vs 10%, respectively, p < 0.001) and non-BRCAlike tumours (median TILs of 10%, p < 0.001). These correlations remained significant within the ER-positive subgroup. Within TNBC, TIL levels were not higher in BRCAlike compared to non-BRCA-like tumours (median TILs of 30% vs 25%, respectively, p ¼ 0.96). In this stage III BC cohort, high TIL level was associated with favourable outcome regarding recurrence-free and overall survival (TILs per 10% increment, HR 0.82, 95% CI 0.71-0.94, p ¼ 0.01, respectively HR 0.80, 95% CI 0.68-0.94, p ¼ 0.01). There was no significant interaction between TIL levels and benefit of intensified platinum-based chemotherapy. Conclusions: In this high-risk breast cancer cohort, high TILs were associated with TNBC and BRCA1-like status. Within the ER-positive subgroup, TIL levels were higher in BRCA1-like compared to non-BRCA-like tumours, but this was not seen within the TNBC subgroup. When adjusted for clinical characteristics, TIL levels were significantly associated with a more favourable outcome in stage III BC patients. Legal entity responsible for the study: The authors. Funding: Dutch Cancer Society. Disclosure: A. Cimino-Mathews: Research grant / Funding (self): BMS. S.C. Linn: Advisory /