Background

The late occurrence of isolated local recurrence (LR) of luminal BC calls into question whether these are true LR or new primaries. We evaluated the concordance of the mutation profiles between matched primary tumors (PT) and LR.

Methods

We collected data from women with LR of luminal BC treated at Gustave Roussy and Trieste University Hospital between 1992 and 2018. Following a quality control, targeted NGS was performed on the IonTorrent S5 NGS platform with the Oncomine Tumor Mutation Load Assay covering 409 critical oncogenes or tumor suppressor genes to analyze PT and LR samples. For the bioinformatic analysis, we retained the matched samples that passed quality check and had a total mean depth coverage ≥ 300X. Variants were filtered on their allele frequency ≥ 5% and a read count ≥ 5X, and on the basis of their genomic effect and annotation.

Results

Among the 131 eligible patients, 82 matched PT and LR were sequenced and analyzed. The table summarizes patient, PT and LR characteristics. Median time until LR was 6.0 years. After a median follow-up of 4.6 years following LR, median DDFS and OS were 8.1 and 8.7 years, respectively. In the PT, the main genes with more than 20% of variants were KMT2D, ATRX, MTOR, ATM and KMT2A. In the LR, the main genes with more than 10% of variants were KMT2D, NOTCH2, PIK3CA, and KMT2A. The main gene with recurrent mutation present in both PT and LR was PIK3CA (4.8%). This analysis showed that 17 cases (20%) shared the same variants between PT and LR. Table: 18P

Patient and tumor characteristics

Conclusions

Although we found a wide range of molecular alterations in LR, a minority of patients had concordant mutational profiles between PT and LR. These findings, if confirmed in larger studies, may better guide the choice of therapy after LR excision.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Lacroix-Triki: Financial Interests, Advisory Board: Myriad genetics; Financial Interests, Advisory Board: Exact sciences; Financial Interests, Advisory Board: Rroche diagnostics; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Daiichi Sankyo; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: Roche. E. Rouleau: Financial Interests, Invited Speaker: BMS; Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: Roche; Financial Interests, Invited Speaker: Clovis; Financial Interests, Invited Speaker: GSK. L. Lacroix: Financial Interests, Advisory Role: Adept Field Solutions; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Bayer; Financial Interests, Advisory Role: Boehringer; Financial Interests, Advisory Role: BMS; Financial Interests, Advisory Role: Lilly; Financial Interests, Advisory Role: Icomed; Financial Interests, Advisory Role: Genomic Health; Financial Interests, Advisory Role: Medimmune; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: QualWorld; Financial Interests, Advisory Role: Taiho Oncology; Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Thermofisher; Financial Interests, Advisory Role: VelaDx; Financial Interests, Sponsor/Funding: Abbott; Financial Interests, Sponsor/Funding: Amgen; Financial Interests, Sponsor/Funding: AstraZeneca; Financial Interests, Sponsor/Funding: Beckman Coulter; Financial Interests, Sponsor/Funding: Bayer; Financial Interests, Sponsor/Funding: Boeringer; Financial Interests, Sponsor/Funding: BMS; Financial Interests, Sponsor/Funding: Illumina; Financial Interests, Sponsor/Funding: Genomic Health; Financial Interests, Sponsor/Funding: Guardant health; Financial Interests, Sponsor/Funding: Lilly; Financial Interests, Sponsor/Funding: Medimmune; Financial Interests, Sponsor/Funding: Myriad; Financial Interests, Sponsor/Funding: Novartis; Financial Interests, Sponsor/Funding: Pfizer; Financial Interests, Sponsor/Funding: Roche; Financial Interests, Sponsor/Funding: Siemens Healthineer; Financial Interests, Sponsor/Funding: Taiho Oncology; Financial Interests, Sponsor/Funding: Thermofisher; Financial Interests, Sponsor/Funding: VelaDx. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Daiichi; Other, Founder: Pegacsy. B. Pistilli: Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Myriad; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Personal, Sponsor/Funding: AstraZeneca; Financial Interests, Personal, Sponsor/Funding: Pierre Fabre; Financial Interests, Personal, Sponsor/Funding: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo. All other authors have declared no conflicts of interest.

Background

ET represents a cornerstone in the treatment of early and late hormone receptors-positive (HR+) BC. However, adherence to ET is a major issue that can substantially impact survival outcomes. We explored whether PDDI with ET impact adherence.

Methods

We scanned the French version of the THIN™ database for women who had a reported diagnosis of BC and received ET (tamoxifen [tam] or aromatase inhibitor [AI]) between 1994 and 2021. Adherence was measured annually and defined by a medication possession ratio (MPR) ≥ 80% over 1-year prescription period. PDDI was classified using the Claude Bernard Drug Database into absent, minor (combination to take into account), moderate (combination requiring precautions for use), major (combination not recommended) and contraindicated. We used repeated-measure regression models to estimate odds ratios (OR) for the correlation between MPR ≥ 80% and age, baseline comorbidities, PDDI, and MPR during the previous year. Among patients with multiple PDDI, the worse PDDI category by patient was retained and included in the multivariable model.

Results

Among the 10,863 eligible pts, polypharmacy ≥ 5 drugs was reported in 33.7% and 47.8% of the tam and AI cohorts. PDDI occurrence is summarized in the table. PDDI were mostly moderate in the tam (60.4-80.6%) and AI (94.7%-99.3%) cohorts; contraindicated combinations were below 1%. In the tam cohort, annual MPR ≥ 80% was 79.3% (n = 2,824) at year 1 and 89.5% (n = 426) at year 5. The association between MPR ≥ 80% and presence of PDDI was not statistically significant neither in the tam (OR 0.991, 95% CI 0.0.914-1.075) nor AI (OR 1.046, 95% CI 0.954-1.147) cohorts. Table: 225P

Prevalence of PDDI with ET at baseline and during follow up

Conclusions

Adherence to ET was not associated with PDDI in patients with HR+ BC treated with tam or AI.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Bardet: Financial Interests, Personal, Other: Roche SAS. O. Bougacha, L. Gantzer, B. Lekens: Financial Interests, Full or part-time Employment: Cegedim R&D. I.V. Luis: Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Pfizer/Edimark; Financial Interests, Institutional, Invited Speaker: Pfizer/Edimark; Financial Interests, Institutional, Invited Speaker: AstraZeneca. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Pierre Fabre, Orion, Sanofi, Rappta, Cellectis, Isis/Servier; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Seagen, Lilly, AstraZeneca, MSD, Roche Genentech, BMS, Puma, Orion, Sanofi; Financial Interests, Institutional, Advisory Board, Ad Board: Besins Healthcare; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker, Clinical Research Funding to my Institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Other, Founder: Pegacsy. S. Michiels: Financial Interests, Personal, Other, Statistical advice: IDDI, Amaris, Roche; Financial Interests, Personal, Other, DSMB member: Sensorion, Servier, Biophytis, Yuhan. B. Pistilli: Financial Interests, Institutional, Advisory Role: AstraZeneca, Pfizer, Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Myriad, Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Novartis, Puma; Financial Interests, Personal, Sponsor/Funding: AstraZeneca, Pierre Fabre, MSD. All other authors have declared no conflicts of interest.

Background

The late occurrence of isolated local recurrence (LR) of luminal BC calls into question whether these are true LR or new primaries. We evaluated the concordance of the mutation profiles between matched primary tumors (PT) and LR.

Methods

We collected data from women with LR of luminal BC treated at Gustave Roussy and Trieste University Hospital between 1992 and 2018. Following a quality control, targeted NGS was performed on the IonTorrent S5 NGS platform with the Oncomine Tumor Mutation Load Assay covering 409 critical oncogenes or tumor suppressor genes to analyze PT and LR samples. For the bioinformatic analysis, we retained the matched samples that passed quality check and had a total mean depth coverage ≥ 300X. Variants were filtered on their allele frequency ≥ 5% and a read count ≥ 5X, and on the basis of their genomic effect and annotation.

Results

Among the 131 eligible patients, 82 matched PT and LR were sequenced and analyzed. The table summarizes patient, PT and LR characteristics. Median time until LR was 6.0 years. After a median follow-up of 4.6 years following LR, median DDFS and OS were 8.1 and 8.7 years, respectively. In the PT, the main genes with more than 20% of variants were KMT2D, ATRX, MTOR, ATM and KMT2A. In the LR, the main genes with more than 10% of variants were KMT2D, NOTCH2, PIK3CA, and KMT2A. The main gene with recurrent mutation present in both PT and LR was PIK3CA (4.8%). This analysis showed that 17 cases (20%) shared the same variants between PT and LR. Table: 18P

Patient and tumor characteristics

Conclusions

Although we found a wide range of molecular alterations in LR, a minority of patients had concordant mutational profiles between PT and LR. These findings, if confirmed in larger studies, may better guide the choice of therapy after LR excision.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Lacroix-Triki: Financial Interests, Advisory Board: Myriad genetics; Financial Interests, Advisory Board: Exact sciences; Financial Interests, Advisory Board: Rroche diagnostics; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Daiichi Sankyo; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: Roche. E. Rouleau: Financial Interests, Invited Speaker: BMS; Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: Roche; Financial Interests, Invited Speaker: Clovis; Financial Interests, Invited Speaker: GSK. L. Lacroix: Financial Interests, Advisory Role: Adept Field Solutions; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Bayer; Financial Interests, Advisory Role: Boehringer; Financial Interests, Advisory Role: BMS; Financial Interests, Advisory Role: Lilly; Financial Interests, Advisory Role: Icomed; Financial Interests, Advisory Role: Genomic Health; Financial Interests, Advisory Role: Medimmune; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: QualWorld; Financial Interests, Advisory Role: Taiho Oncology; Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Thermofisher; Financial Interests, Advisory Role: VelaDx; Financial Interests, Sponsor/Funding: Abbott; Financial Interests, Sponsor/Funding: Amgen; Financial Interests, Sponsor/Funding: AstraZeneca; Financial Interests, Sponsor/Funding: Beckman Coulter; Financial Interests, Sponsor/Funding: Bayer; Financial Interests, Sponsor/Funding: Boeringer; Financial Interests, Sponsor/Funding: BMS; Financial Interests, Sponsor/Funding: Illumina; Financial Interests, Sponsor/Funding: Genomic Health; Financial Interests, Sponsor/Funding: Guardant health; Financial Interests, Sponsor/Funding: Lilly; Financial Interests, Sponsor/Funding: Medimmune; Financial Interests, Sponsor/Funding: Myriad; Financial Interests, Sponsor/Funding: Novartis; Financial Interests, Sponsor/Funding: Pfizer; Financial Interests, Sponsor/Funding: Roche; Financial Interests, Sponsor/Funding: Siemens Healthineer; Financial Interests, Sponsor/Funding: Taiho Oncology; Financial Interests, Sponsor/Funding: Thermofisher; Financial Interests, Sponsor/Funding: VelaDx. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Daiichi; Other, Founder: Pegacsy. B. Pistilli: Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Myriad; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Personal, Sponsor/Funding: AstraZeneca; Financial Interests, Personal, Sponsor/Funding: Pierre Fabre; Financial Interests, Personal, Sponsor/Funding: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo. All other authors have declared no conflicts of interest.

Background

ET represents a cornerstone in the treatment of early and late hormone receptors-positive (HR+) BC. However, adherence to ET is a major issue that can substantially impact survival outcomes. We explored whether PDDI with ET impact adherence.

Methods

We scanned the French version of the THIN™ database for women who had a reported diagnosis of BC and received ET (tamoxifen [tam] or aromatase inhibitor [AI]) between 1994 and 2021. Adherence was measured annually and defined by a medication possession ratio (MPR) ≥ 80% over 1-year prescription period. PDDI was classified using the Claude Bernard Drug Database into absent, minor (combination to take into account), moderate (combination requiring precautions for use), major (combination not recommended) and contraindicated. We used repeated-measure regression models to estimate odds ratios (OR) for the correlation between MPR ≥ 80% and age, baseline comorbidities, PDDI, and MPR during the previous year. Among patients with multiple PDDI, the worse PDDI category by patient was retained and included in the multivariable model.

Results

Among the 10,863 eligible pts, polypharmacy ≥ 5 drugs was reported in 33.7% and 47.8% of the tam and AI cohorts. PDDI occurrence is summarized in the table. PDDI were mostly moderate in the tam (60.4-80.6%) and AI (94.7%-99.3%) cohorts; contraindicated combinations were below 1%. In the tam cohort, annual MPR ≥ 80% was 79.3% (n = 2,824) at year 1 and 89.5% (n = 426) at year 5. The association between MPR ≥ 80% and presence of PDDI was not statistically significant neither in the tam (OR 0.991, 95% CI 0.0.914-1.075) nor AI (OR 1.046, 95% CI 0.954-1.147) cohorts. Table: 225P

Prevalence of PDDI with ET at baseline and during follow up

Conclusions

Adherence to ET was not associated with PDDI in patients with HR+ BC treated with tam or AI.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Bardet: Financial Interests, Personal, Other: Roche SAS. O. Bougacha, L. Gantzer, B. Lekens: Financial Interests, Full or part-time Employment: Cegedim R&D. I.V. Luis: Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Pfizer/Edimark; Financial Interests, Institutional, Invited Speaker: Pfizer/Edimark; Financial Interests, Institutional, Invited Speaker: AstraZeneca. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Pierre Fabre, Orion, Sanofi, Rappta, Cellectis, Isis/Servier; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Seagen, Lilly, AstraZeneca, MSD, Roche Genentech, BMS, Puma, Orion, Sanofi; Financial Interests, Institutional, Advisory Board, Ad Board: Besins Healthcare; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker, Clinical Research Funding to my Institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Other, Founder: Pegacsy. S. Michiels: Financial Interests, Personal, Other, Statistical advice: IDDI, Amaris, Roche; Financial Interests, Personal, Other, DSMB member: Sensorion, Servier, Biophytis, Yuhan. B. Pistilli: Financial Interests, Institutional, Advisory Role: AstraZeneca, Pfizer, Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Myriad, Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Novartis, Puma; Financial Interests, Personal, Sponsor/Funding: AstraZeneca, Pierre Fabre, MSD. All other authors have declared no conflicts of interest.