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ASCO 2021: Summary Overview and Outlook 15 | Overview of Latest Breast Cancer Research (ER Positive Breast Cancer Column)

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The annual meeting of the American Society of Clinical Oncology (ASCO) will be held from June 4 to 8, 2021.

Breast topic summary: breast cancer topics Summary:Breast Cancer

ASCO 2021: Summary Overview and Outlook 15 | Overview of Latest Breast Cancer Research (ER Positive Breast Cancer Column)

ASCO 2021: Summary Overview and Outlook 11 | Breast Cancer Research Overview (Invasive Breast Cancer Column)

Background: Background:

Method: Method:

Result: Result:

Conclusion: Conclusion:

For details, please refer to: Retrospective cohort study of estrogen receptor low positive early breast cancer using real world data.

Background: Background:

Method: Method:

Result: Result:

Conclusion: Conclusion:

For details, see: For details, see: Clinical validation of EndoPredict in premenopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer

3.
AMEERA-5: A randomized, double-blind phase III study on amcenestrant (SAR439859) + palbociclib and letrozole + palbociclib in the treatment of previously untreated ER+/HER2- advanced breast cancer

Background:
Selective estrogen receptor degradants (SERD) block signal transduction related to estrogen receptor (ER) and have aroused interest in the treatment of patients with advanced ER + breast cancer (BC) (pts).
Fulvestrant is currently the only SERD that can be used for advanced BC, but it requires intramuscular injection, which limits the application dose, exposure and receptor participation.
Amcenestrant (SAR439859) is an oral SERD that can bind wild-type and mutant ER with high affinity, block estradiol binding and promote up to 98% ER degradation in preclinical studies.
In the study of ER + / HER2- advanced BC pretreatment patients in the AMEERA-1 stage, methotrexate 150-600 mg once a day (QD) showed that when the plasma concentration was> 100 ng/mL, the average ER occupancy rate was 94 % And good security (Bardia, 2019; archived data).
As part of the ongoing Phase I study, the combination therapy of amcenestrant + palbociclib (palbo) is also evaluated.
CDK 4/6 inhibitor (CDK4/6i) combined with aromatase inhibitor (AI), which is the gold standard for first-line treatment of advanced breast cancer, can prolong the progression-free survival (PFS) of pts without prior treatment of ER + / HER2- Advanced BC, but has not yet shown OS benefit in postmenopausal patients.
In this case, there is still a need for more effective treatments clinically.
However, the benefit of OS has not been shown in postmenopausal patients.
In this case, there is still a need for more effective treatments clinically.
However, it has not been shown to benefit from OS in postmenopausal patients.
In this case, there is still a need for more effective treatments clinically.

Background: Background:
Selective estrogen receptor degradants (SERD) block the signal transduction related to estrogen receptor (ER) and have aroused interest in the treatment of patients with advanced ER + breast cancer (BC) (pts) .
Fulvestrant is currently the only SERD that can be used for advanced BC, but it requires intramuscular injection, which limits the application dose, exposure and receptor participation.
Amcenestrant (SAR439859) is an oral SERD that can bind wild-type and mutant ER with high affinity, block estradiol binding and promote up to 98% ER degradation in preclinical studies.
In the study of ER + / HER2- advanced BC pretreatment patients in the AMEERA-1 stage, methotrexate 150-600 mg once a day (QD) showed that when the plasma concentration was> 100 ng/mL, the average ER occupancy rate was 94 % And good security (Bardia, 2019; archived data).
As part of the ongoing Phase I study, the combination therapy of amcenestrant + palbociclib (palbo) is also evaluated.
CDK 4/6 inhibitor (CDK4/6i) combined with aromatase inhibitor (AI), which is the gold standard for first-line treatment of advanced breast cancer, can prolong the progression-free survival (PFS) of pts without prior treatment of ER + / HER2- Advanced BC, but has not yet shown OS benefit in postmenopausal patients.
In this case, there is still a need for more effective treatments clinically.
However, the benefit of OS has not been shown in postmenopausal patients.
In this case, there is still a need for more effective treatments clinically.
However, it has not been shown to benefit from OS in postmenopausal patients.
In this case, there is still a need for more effective treatments clinically.

method:
AMEERA-5 (NCT04478266) is an ongoing prospective, randomized, double-blind phase III study comparing amcenestrant + palbo and letrozole + palbo in patients with advanced, locally recurring, or metastatic ER+/HER2- BC Efficacy and safety have not received systemic treatment for advanced disease before.
The study included men, premenopausal/perimenopausal (using goserelin), and postmenopausal women.
Exclude patients who progressed during or within 12 months of (neo) adjuvant endocrine therapy using any of the following drugs: AI, selective estrogen receptor modulators, CDK4/6i.
Patients were randomly assigned 1:1 to either continuous oral 200 mg or letrozole 2.
5 mg QD and a matching placebo; both were combined with oral palbo 125 mg QD (d1-21 every 28 days).
Randomization was stratified according to disease type (new-onset and recurrent disease), presence of visceral metastasis, and menopausal status.
The primary endpoint is the investigator-assessed progression-free survival (PFS) (RECIST v1.
1).
Secondary endpoints are overall survival, PFS2, objective response rate, duration of response, clinical benefit rate, amceestrant and palbo pharmacokinetics, health-related quality of life, chemotherapy time, and safety.
Over time, biomarkers will be measured in paired tumor biopsies and cell-free deoxyribonucleic acid (cfDNA).
Target enrollment rate = 1066 points; enrollment as of January 2021 = 33 points.
Bardia A et al.
, secondary endpoints are overall survival, PFS2, objective response rate, duration of response, clinical benefit rate, amceestrant and palbo pharmacokinetics, health-related quality of life, chemotherapy time and safety.
Over time, biomarkers will be measured in paired tumor biopsies and cell-free deoxyribonucleic acid (cfDNA).
Target enrollment rate = 1066 points; enrollment as of January 2021 = 33 points.
Bardia A et al.
, secondary endpoints are overall survival, PFS2, objective response rate, duration of response, clinical benefit rate, amceestrant and palbo pharmacokinetics, health-related quality of life, chemotherapy time and safety.
Over time, biomarkers will be measured in paired tumor biopsies and cell-free deoxyribonucleic acid (cfDNA).
Target enrollment rate = 1066 points; enrollment as of January 2021 = 33 points.

For details, see: AMEERA-5: A randomized, double-blind phase III study of amcenestrant (SAR439859) + palbociclib versus letrozole + palbociclib for previously untreated ER+/HER2- advanced breast cancer For details: For details, see:AMEERA-5: A randomized, double-blind phase III study of amcenestrant (SAR439859) + palbociclib versus letrozole + palbociclib for previously untreated ER+/HER2- advanced breast cancer

4.
LY3484356, the first human phase 1a/b trial of an oral selective estrogen receptor (ER) degrading agent (SERD) in ER+ advanced breast cancer (aBC) and endometriotic cancer (EEC): EMBER Research results

Background:
New degraders and antagonists of ER are being evaluated in aBC to overcome ER-mediated resistance and the bioavailability and dose limitations of Fulvestrant (the only approved SERD).
ER is also overexpressed in 80% of EECs, and these patients (pts) use endocrine therapy (ET).
LY3484356 is a new type of oral bioavailable SERD with pure antagonistic properties and can continuously inhibit ER-dependent gene transcription and cell growth.
Before the clinic, LY3484356 showed good efficacy and pharmacokinetic (PK) properties, including anti-tumor activity in ESR1 mutants.
Here, we show the initial clinical data from EMBER, which is the first human phase 1a/b trial of this new drug.

Background: Background:

Methods:
Phase 1a assessed the LY3484356 dose escalation (i3 + 3 design) for women with ER +, HER2-aBC (previous therapies for aBC with ≤3 protocol modification; previous ET sensitivity) and ER + EEC (pre-platinum therapy) ).
Premenopausal women received concomitant GnRH agonists.
Key endpoints include determining the recommended phase 2 dose, safety and tolerability, PK, and objective response rate and clinical benefit rate according to RECIST v1.
1.

Method: Method:

Results:
As of the data cutoff (November 9, 2020), 28 patients (n = 24 aBC, n = 4 EEC) were enrolled in the dose range of 200-1200 mg QD.
The median age is 59 years (range 35-80).
The median of previous treatments for aBC was 2 (range, 1-8; 6 patients enrolled before the protocol revision received ≥4 previous treatments), including previous fulvestrant (46%), CDK4/6 inhibition Drugs (83%) and chemotherapy (33%).
No dose limiting toxicity was observed.
Adverse events (TEAE) during treatment were mostly grade 1-2, including nausea (32%), fatigue (25%), and diarrhea (18%).
The only grade 3 treatment-related AE was diarrhea (n = 1).
Despite intensive central ECG monitoring, no bradycardia and QTc prolonged TEAE were observed.
A proportional increase in the exposure dose of LY3484356 was observed for 25-30 hours in all assessed doses and t 1/2.
At the starting dose level (200 mg QD), the exposure of unconjugated LY3484356 exceeded the exposure achieved with fulvestrant.
16 of the 28 patients can be evaluated for efficacy, and the remaining 12 patients are still in progress before the first scan.
Of the 16 evaluable patients, 11 (8 aBC, 3 EEC) are in stable condition (10 are ongoing), and 5 are progressing.
The response of RECIST was observed after data reduction and will be explained in detail at the meeting.
Plasma ctDNA analysis showed a reduction in the frequency of mutant alleles, including 9/12 (75%) of all dose levels to assess mutant ESR1 in patients.

Result: Result:

Conclusion: The
administration of LY3484356 QD shows good safety and PK characteristics, as well as preliminary efficacy for severely pretreated ER+ aBC and EEC patients.
The updated data will be announced at the meeting.

Conclusion: Conclusion:

For details, see: A first-in-human phase 1a/b trial of LY3484356, an oral selective estrogen receptor (ER) degrader (SERD) in ER+ advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): Results from the EMBER study

For details, see: For details, see: For details, see:A first-in-human phase 1a/b trial of LY3484356, an oral selective estrogen receptor (ER) degrader (SERD) in ER+ advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC) : Results from the EMBER study

5.
SERENA-4: Phase 3 comparison of AZD9833 (camizestrant) plus palbociclib and anastrozole plus palbociclib for patients with ER-positive and HER2-negative advanced breast cancer who have not previously been treated for systemic diseases

Background:
More than two-thirds of advanced breast cancer (ABC) patients have estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) tumors.
Current standard first-line treatments include aromatase inhibitors (AI) or fulvestrant, selective endoplasmic reticulum degradants (SERD), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.
For men with ABC and premenopausal women, it is recommended to use luteinizing hormone releasing hormone (LHRH) agonists at the same time.
Despite this, almost all ABCs eventually develop resistance to endocrine therapy (ET), and the disease is incurable.
New therapies are needed to combat ET resistance, maintain patient quality of life (QoL), and delay the need for chemotherapy.
AZD9833 (camizestrant) is an oral bioavailable, highly effective, et al.
, 2020).
A phase I study (SERENA-1) has demonstrated that AZD9833 is well tolerated and has good anti-tumor properties when administered alone or in combination with palbociclib (a CDK4/6 inhibitor) (Baird Etc.
, SABCS 2020).
SERENA-4 (NCT04711252) is a randomized, multicenter, double-blind, phase III trial designed to evaluate the safety and safety of AZD9833 and Palbociclib in patients with ER+ HER2-ABC who have not received any systemic therapy in the context of advanced disease.
Effectiveness.

Background: Background:
More than two-thirds of advanced breast cancer (ABC) patients have estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) tumors.
Current standard first-line treatments include aromatase inhibitors (AI) or fulvestrant, selective endoplasmic reticulum degradants (SERD), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.
For men with ABC and premenopausal women, it is recommended to use luteinizing hormone releasing hormone (LHRH) agonists at the same time.
Despite this, almost all ABCs eventually develop resistance to endocrine therapy (ET), and the disease is incurable.
New therapies are needed to combat ET resistance, maintain patient quality of life (QoL), and delay the need for chemotherapy.
AZD9833 (camizestrant) is an oral bioavailable, highly effective, et al.
, 2020).
A phase I study (SERENA-1) has demonstrated that AZD9833 is well tolerated and has good anti-tumor properties when administered alone or in combination with palbociclib (a CDK4/6 inhibitor) (Baird Etc.
, SABCS 2020).
SERENA-4 (NCT04711252) is a randomized, multicenter, double-blind, phase III trial designed to evaluate the safety and safety of AZD9833 and Palbociclib in patients with ER+ HER2-ABC who have not received any systemic therapy in the context of advanced disease.
Effectiveness.

Methods:
SERENA-4 will recruit 1342 patients with de novo or recurrent ER+HER2–ABC who have not previously received systemic treatment for local recurrence or metastatic disease.
Patients who relapse must receive adjuvant AI or tamoxifen for at least 24 months without recurrence.
Patients will be randomized 1:1 to receive oral (a) AZD9833 (75 mg, once a day), palbociclib (125 mg, once a day for 21 days, then stop the drug for 7 days) and an anastrozole-matched placebo ( Once a day) or (b) Anastrozole (1 mg, once a day), palbociclib (same as the active group) and AZD9833 matched placebo (once a day).
Premenopausal women and men will also receive LHRH agonists.
The primary endpoint will be progression-free survival (PFS; up to 5 years).
Secondary endpoints will include overall survival (up to 8 years), the length of the second PFS period, objective response, chemotherapy time, and changes in QoL indicators.

For details, see: SERENA-4: A phase 3 comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease.
For details, see: For details, see:SERENA-4: A phase 3 comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease

6.
In the NA-PHER2 trial, ER and immune-related characteristics define the benefits of palbociclib, trastuzumab, pertuzumab +/- fulvestrant for patients with ER+/HER2+ breast cancer

Background:
In the NA-PHER2 study, we evaluated the association between biological pathways and pathological complete response (pCR) and Ki67 downregulation.

Background: Background:

Methods:
Centrally diagnosed ER + (> 10%) HER2 + breast cancer (BC) patients were treated with neoadjuvant trastuzumab, pertuzumab, and palbocilib in two independent non-randomized cohorts, (Fulv , N = 30) or not used (NoFulv, n = 28) Fulvestrant (+/-LHRH analogue).
We assessed the pre-treatment [n = 53/58 (91.
4%)], day 14 [n = 49/58 (84.
5%)] and surgical residual lesions [n = 42/45 (93.
3%)].
We studied biomarker kinetics and the association with down-regulation of pCR or Ki67 (focused evaluation) on day 14 and at the time of surgery.
In the entire population and each cohort, we mainly evaluated three predefined biomarkers (ER-metagene [from OncotypeDX], CD8-metagene and ERBB2 expression), and then we explored a list of predefined gene sets.

Method: Method:

Results:
In the biomarker population, the pCR rate was 22.
5% (28.
6% and 16.
0% in the Fulv and NoFulv cohorts, respectively).
At baseline, continuous CD8-metagene (OR 1.
85 [1.
12-3.
06], p = 0.
016) and ER-metagene (OR 0.
56 [0.
34-0.
90], p = 0.
016) were associated with higher and lower pCR rates, respectively.
High ERBB2 (above the median) was slightly associated with pCR (OR 3.
83 [0.
90-16.
3], p = 0.
068).
Only the ER and CD8 metagenes remained significant in the multivariate analysis and had similar predictive properties in the two cohorts.
Combining categorical variables, the pCR rates of the high CD8/low ER and low CD8/high ER groups were 61.
5% and 0%, respectively, while the low CD8/low ER and high CD8/high ER pCR rates were similar to 15% pCR (p = 0.
001 ).
This association was significant in both cohorts (p = 0.
019 Fulv; p = 0.
028 NoFulv).
The dynamic evaluation of the same biomarker on day 14 did not improve the prediction.
Only in the Fulv cohort (p = 0.
016), higher ER-metagene at baseline (but not CD8 and ERBB2) was associated with a strong down-regulation of Ki67 on day 14 (Ki67 <2.
7%, complete cell cycle arrest).
ER-metagene was also associated with downregulation of Ki67 retained during surgery (Ki67 <10%) (p = 0.
002).
Alternative ER and immune-related features provide very similar results.
A comprehensive overview of complex molecular dynamics and exploratory links to the results will be introduced.

Result: Result:

Conclusion:
In ER+/HER2+ BC, the low expression of ER-related genes and the high expression of immune-related genes identify patients with a very high probability of achieving pCR with no chemotherapy.
In the fulvestrant cohort, although the pCR rate was lower, the group with higher ER-metagene levels still had a higher Ki67 downregulation on day 14, which was related to the long-term benefit of luminal tumors.
These findings provide a potential tool for tailored downgrade strategies.

Conclusion: Conclusion:

For details, see: ER and immune-related signatures define benefit to palbociclib, trastuzumab, pertuzumab +/- fulvestrant in ER+/HER2+ breast cancer patients in the NA-PHER2 trial

For details, see: For details, see: For details, see:ER and immune-related signatures define benefit to palbociclib, trastuzumab, pertuzumab +/- fulvestrant in ER+/HER2+ breast cancer patients in the NA-PHER2 trial

7.
Using 80 gene features to classify genomic high-risk ER+HER2- breast cancer tumors into functional basal type or endoscopic B type molecular profile

background:

Background: Background:

80 gene signatures (BluePrint/BP) classify early breast cancer as cavity type, HER2 type or Basal type according to functional molecular pathways.
In the NBRST study, 13% of immunochemical (IHC)-defined ER+HER2- cancers were reclassified as Basal (ER+ Basal) by BP testing.
These people had a poorer prognosis, but were more responsive to neoadjuvant chemotherapy.
It is good for ER+HER2-cancer of genomic cavity type.
The 70-gene recurrence risk feature (MammaPrint/MP) further stratifies laparoscopic cancer into low-risk laparoscopic type A or high-risk (HR) laparoscopic type B, and HR type cancer can be further stratified as high 1 Type (H1) or high type 2 (H2), the I-SPY2 test showed that ER+ cancers classified as H2 have a higher pCR rate.
Here, we studied the biological differences between ER+ basal carcinoma, ER-basal carcinoma, H1 cavity B carcinoma and H2 cavity B carcinoma through whole transcriptome analysis.

method:

Method: Method:

In the FLEX study (NCT03053193), 1501 cases of breast cancer with known IHC ER status were classified according to MP and BP: 103 cases of ER+ base, 210 cases of ER-base and 1188 lumen B (H1 n=1034, H2 n=154 ).
Clinical factors are assessed by chi-square test or Fisher's exact test; analysis of variance or t- test is used to analyze age.
Use Limma to detect differentially expressed genes (DEG) and use GSEA for pathway analysis.
DEGs with a fold change> 2 and FDR <0.
05 are considered significant.

Results:
Basal cancer (ER+/ER-) is larger and higher grade than luminal B cancer.
Cluster analysis showed that the transcription profiles between ER+ basal and ER-basal cancers were similar, and different from luminal B cancers.
Few DEG was detected between ER+ basal carcinoma and ER-basal carcinoma, and significantly more DEG was found between ER+ basal carcinoma and luminal B carcinoma.
Compared with ER-Basal cancer, only three up-regulated genes were detected in ER+ Basal: ESR1 and two immune-related genes (FDCSP and LTF).
The enrichment analysis of DEGs showed that immune activation and cell proliferation increased in ER+ basal and ER-basal carcinomas, and decreased the estrogen response between ER+ basal and luminal B carcinomas.
Enrichment analysis between luminal B H1 and H2 cancers shows that H2 cancers have higher immune activation and cell proliferation, and lower estrogen response.

Result: Result:

Conclusion:
The reclassification of ER+ HER2- cancers defined by IHC by BP has determined a subgroup of ER+ cancers, which is biologically closer to ER-Basal than luminal cancers.
The significant difference in the response of ER+ basal and luminal B breast cancer to neoadjuvant chemotherapy supports the clinical importance of these findings.
These data explain the poor prognosis observed in patients with ER+ basal carcinoma and suggest that optimized chemotherapy, such as chemotherapy for triple-negative cancer, may be beneficial.
BP provides clinically actionable information beyond pathological subtypes and can guide neoadjuvant treatment recommendations.

Conclusion: Conclusion:

For details, see: Molecular profiles of genomically high risk ER+ HER2- breast cancer tumors classified as functionally basal or luminal B by the 80-gene signature

For details see: For details see: For details see:Molecular profiles of genomically high risk ER+ HER2- breast cancer tumors classified as functionally basal or luminal B by the 80-gene signature

8.
H3B-6545, a new type of selective estrogen receptor covalent antagonist (SERCA), for estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer Phase I/II studies

Background:
H3B-6545 is a selective small molecule covalent antagonist of ERα, showing preclinical and preliminary clinical activity against ER+ breast cancer (Hamilton EP, SABCS, 2020).
This study evaluated the activity and tolerability of H3B-6545 in endocrine therapy refractory metastatic ER+, HER2- breast cancer patients (pts).

Background: Background:

Methods: The
patient received H3B-6545 once a day, and the recommended phase II dose was 450 mg.
The main goal of Phase II is to estimate the objective response rate (ORR), progression-free survival (PFS), and clinical benefit rate (CBR).
The secondary goals include safety.

Method: Method:

result:

Result: Result:

In the second phase of the trial, 83 patients received the 450 mg treatment.
In addition, 11 patients received 450 mg of treatment in the first phase of the trial and were included in this analysis.
The median age was 62 years (range: 38 to 87 years), 81% had liver and/or lung metastases, and the median of previously treated metastatic disease was 3 (range: 1 to 8).
85%, 80%, 72%, and 50% of patients received CDK4/6 inhibitors, aromatase inhibitors, fulvestrant, and chemotherapy.
Fifty-eight patients (62%) had ESR1 mutations detected in liquid biopsy, including 10 (11%) and 19 patients (20%) with clonal Y537S and clonal D538G mutations, respectively.
As of January 29, 2021, of the reported grade 2 or higher adverse events (AE), ≥10% were anemia (19%), fatigue (16%), nausea (17%) and diarrhea (12%) .
The laboratory grade 2 or above abnormalities reported in ≥10% of patients were decreased creatinine clearance (38%), decreased hemoglobin (37%), increased bilirubin (12%), increased ALT (14%), AST increased (13%), and creatinine increased (11%).
34% reported grade 1 sinus bradycardia (asymptomatic) AE, and 5% reported grade 2 (symptomatic, no intervention required).
Two and three patients reported grade 2 and grade 3 QTcF prolongation, respectively.
There were no treatment-related deaths.
The curative effect is estimated in the table below.
Responses were observed in severely preconditioned patients, patients with visceral metastases, and patients who had previously received fulvestrant, CDK4/6 inhibitors, and/or metastatic therapy.

in conclusion:

Conclusion: Conclusion:

H3B-6545 has controllable safety, and shows single-agent anti-tumor activity in severely pretreated ER+ and HER2-mBC patients.
Clinical activity is observed in patients with ESR1 mutations.

For details, see: Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer

For details see: For details see: For details see:Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer

9.
Efficacy of AI and palbociclib in ER+HER2-advanced breast cancer patients who relapsed during adjuvant tamoxifen treatment: an exploratory analysis of the PADA-1 trial

background:

Background: Background:

In PADA-1 (NCT03079011), a phase III trial to test the clinical utility of ESR1 mutation detection, ER+HER2-advanced breast cancer patients (ABC pts) received aromatase inhibitors (AI) and Palbociclib (Pal) +/- LHRH Agonists are used as first-line treatment.
PADA-1 is open to "AI sensitive" patients, including patients with new stage IV disease or metastasis and recurrence after adjuvant endocrine therapy, and patients with metastasis and recurrence during adjuvant tamoxifen (TAM).
In this auxiliary analysis, we report the efficacy of AI+PAL as a first-line treatment in patients with adjuvant TAM recurrence.

：

：：

PADA-1 ：ER+ HER2- ABC ， ABC AI AI 12 TAM。

：

：：

2017420191，PADA-11017ABC，115（11.
3%）TAM（TAM（N = 112）TAM+GnRH（N = 3））。46（25-81），58（50.
4%）。TAM，AI+PALPFS20.
4（95%CI16.
1；27.
8）。，，PFS30.
6（95%CI26.
7;）27.
8（95%CI24.
1;30.
）】。TAM，TAMPFS（11.
495%CI[8.
7;20.
7]）TAM（23.
895%CI[20.
2;]）。

：

：：

， AI+CDK4/6 TAM 。 AI + PAL PFS ， AI + PAL TAM 。

：Efficacy of AI and palbociclib in ER+ HER2- advanced breast cancer patients relapsing during adjuvant tamoxifen: An exploratory analysis of the PADA-1 trial

：：：Efficacy of AI and palbociclib in ER+ HER2- advanced breast cancer patients relapsing during adjuvant tamoxifen: An exploratory analysis of the PADA-1 trial

10.
21- 70 T1N0 ER/PR+ HER2-

：
CALGB 9343 ， (BCS) (ET) 70 T1N0 ER/PR+ HER2- (RT) 。 21 RT-PCR (RS) ，、HER2 、，。RS BCS (RT) ，。≥70 T1N0 ER/PR+ HER2- RS BCS RT 。

：：

：
(NCDB) (2004-2017) ≥70 ， pT1N0 ER+ PR+ HER2- ， BCS ET ， RS。 RS （ [LR] = 1-10， [IR] = 11-25， [HR] = 26-99）。， (PSM)， 1:1 。 Kaplan-Meier (OS)。 Cox (UVA) (MVA) ， OS 。

：：

：
13,614：LR3,840，IR8,383，HR1,391。 79% RT：LR 77%、IR 79% HR 85%。 PSM HR ， IR HR (IRHR) 。PSM ，， RT 5 OS 90%， 88%（p = 0.
03）。LR 5 OS 89%， 89%（p = 0.
517）。 IRHR ， 5 OS 93%， 5 OS 88%（p = 0.
004）。 MVA ，RT（p = 0.
037） OS ，（p < 0.
001）CDCC （p < 0.
001）OS。 LR MVA ，RT (p = 0.
602) OS 。， IRHR MVA ，RT（p = 0.
004） OS 。

：：

：
RS 。 IRHR RS OS ， LR RS 。， RS ≥ 11 RS 。

：：

：Role of 21- gene recurrence score in patients age ≥70 with T1N0 ER/PR+ HER2- breast cancer treated with breast-conserving surgery and endocrine therapy

：：：Role of 21- gene recurrence score in patients age ≥70 with T1N0 ER/PR+ HER2- breast cancer treated with breast-conserving surgery and endocrine therapy

，~

，~，~

ASCO：https://meeting.
medsci.
cn/ASCO2020

https://meeting.
medsci.
cn/ASCO2020

：https://meetinglibrary.
asco.
org/results?meetingView=2021%20ASCO%20Annual%20Meeting

https://meetinglibrary.
asco.
org/results?meetingView=2021%20ASCO%20Annual%20Meeting

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