Development of a Prognostic Tool to Guide the Decision to Extend Adjuvant Aromatase Inhibitors for up to Ten Years in Postmenopausal Early Breast Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Patients and Methods
2.1. BERENIS Database
2.2. Study Population and Objectives
2.3. Statistical Analysis
3. Results
3.1. Patient Characteristics and Management
3.2. Pattern and Management of Patients Who Relapsed after Five Years of AIs
3.3. Clinical Factors Associated with Recurrence after Five Years of AIs
3.4. Integration of Clinical Variables to Develop a Prognostic Tool
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristics | N | % |
---|---|---|
Age | ||
Mean (years) | 63.3 | |
Median (range) | 63 (33–88) | |
<50 yrs. | 11 | 1 |
50–70 yrs. | 897 | 81.2 |
>70 yrs. | 197 | 17.8 |
Tumor size | ||
pT0 | 3 | 0.3 |
pT1 | 858 | 77.6 |
pT2 | 228 | 20.6 |
pT3 | 16 | 1.4 |
Nodal status | ||
pN0 | 817 | 73.9 |
pN1 | 218 | 19.7 |
pN2 | 57 | 5.2 |
pN3 | 13 | 1.2 |
Micrometastasis | ||
Yes | 97 | 8.8 |
No | 1010 | 91.2 |
Hormone Receptor | ||
Estrogen Receptor + | 1100 | 99.5 |
Estrogen Receptor − | 5 | 0.5 |
Progesterone Receptor + | 855 | 77.4 |
Progesterone Receptor − | 250 | 22.6 |
HER2 status | ||
Positive | 72 | 6.5 |
Negative | 988 | 89.4 |
Histological subtype | ||
Ductal carcinoma | 839 | 76 |
Lobular carcinoma | 197 | 17.8 |
Mix | 27 | 2.4 |
Other | 42 | 3.8 |
Elston–Ellis grade | ||
I | 327 | 29.6 |
II | 584 | 52.8 |
III | 135 | 12.2 |
Tubule formation | ||
1 | 126 | 11.4 |
2 | 331 | 30 |
3 | 579 | 52.4 |
Nuclear polymorphism | ||
1 | 14 | 1.3 |
2 | 733 | 66.3 |
3 | 289 | 26.2 |
Mitotic activity | ||
1 | 801 | 72.5 |
2 | 158 | 14.3 |
3 | 78 | 7.1 |
Emboli | ||
Yes | 165 | 14.9 |
No | 927 | 83.9 |
Surgery | ||
Radical | 313 | 28.3 |
Conservative | 791 | 71.6 |
Chemotherapy | ||
Neoadjuvant | 77 | 6.9 |
Adjuvant | 397 | 35.9 |
No | 632 | 57.2 |
Chemotherapy drug | ||
Anthracycline | 442 | 93.4 |
Cyclophosphamide | 457 | 96.6 |
Taxane | 370 | 78.2 |
Clinical trial | 50 | 10.6 |
Endocrine therapy drug | ||
Anastrozole | 634 | 57.4 |
Letrozole | 284 | 25.7 |
Exemestane | 187 | 16.9 |
Characteristics of Relapses | N | % |
---|---|---|
Age | ||
Mean (years) | 62.7 | |
Median (range) | 62 (39–83) | |
<50 yrs. | 1 | 1 |
50–70 yrs. | 88 | 80.7 |
>70 yrs. | 20 | 18.3 |
Location | ||
Locoregional | 9 | 8.3 |
Contralateral | 29 | 26.6 |
Metastasis | 71 | 65.1 |
Histology | ||
Invasive ductal carcinoma | 69 | 63.3 |
Invasive lobular carcinoma | 15 | 14 |
In situ | 7 | 6.4 |
Time to relapse after five years of AIs | ||
Median (range) | 31 (17–51) | |
First metastasis location | ||
Single | n = 34 | 47.9 |
Bone | 16 | |
Pleural | 6 | |
Hepatic | 4 | |
Cutaneous | 3 | |
Brain and SNC | 2 | |
Pulmonary | 1 | |
Osteomedullary invasion | 1 | |
Lymph node involvement | 1 | |
Multiple, including: | n = 37 | 52.1 |
Bone | 25 | |
Hepatic | 9 | |
Lymph node involvement | 9 | |
Pleural | 8 | |
Pulmonary | 8 | |
Cutaneous | 6 | |
Brain and SNC | 3 | |
Peritoneal | 3 | |
Ovarian | 1 | |
Osteomedullary invasion | 1 | |
Management for metastatic relapse | ||
Chemotherapy | 11 | 15.5 |
Hormonotherapy alone | 38 | 53.5 |
Hormonotherapy and metabolic targeted therapy | 17 | 23.9 |
Best supportive care only | 5 | 7.1 |
Characteristics | Univariate Analysis | Multivariate Analysis | ||||||
---|---|---|---|---|---|---|---|---|
Hazard Ratio | p > |z| | 95% CI | Hazard Ratio | p > |z| | 95% CI | |||
Age ≥ 70 yrs. vs. <70 yrs. | 1.64 | 0.036 | 1.03 | 2.61 | 1.68 | 0.033 | 1.04 | 2.69 |
Age (continuous) | 1.01 | 0.382 | 0.99 | 1.04 | ||||
Number of macrometastases (continuous) | 1.18 | 0.000 | 1.13 | 1.23 | 1.13 | 0.000 | 1.08 | 1.20 |
Tumor size (continuous) | 1.02 | 0.000 | 1.02 | 1.03 | ||||
pT 2–3 vs. 0–1 | 2.77 | 0.000 | 1.89 | 4.05 | 1.58 | 0.060 | 0.98 | 2.55 |
Tumor grade II vs. I | 1.27 | 0.327 | 0.79 | 2.06 | ||||
Tumor grade III vs. I | 1.90 | 0.039 | 1.03 | 3.51 | ||||
Tumor grade III vs. I–II | 1.62 | 0.065 | 0.97 | 2.71 | ||||
Nuclear pleomorphism | 0.94 | 0.799 | 0.59 | 1.50 | ||||
Tubule formation 2–3 vs. 1 | 4.05 | 0.017 | 1.28 | 12.80 | 2.28 | 0.18 | 0.68 | 7.68 |
Mitotic activity 2–3 vs. 1 | 2.43 | 0.000 | 1.60. | 3.68 | 1.89 | 0.009 | 1.18 | 3.05 |
Number of micrometastases | 1.54 | 0.11 | 0.91 | 2.63 | ||||
ER and PR dissociation vs. no | 0.93 | 0.76 | 0.60 | 1.45 | ||||
HER2 overexpressed vs. no | 0.75 | 0.49 | 0.33 | 1.71 | ||||
Emboli 0 vs. positive | 1.92 | 0.003 | 1.25 | 2.94 | 1.15 | 0.564 | 0.72 | 1.84 |
Lobular histology vs. other | 1.60 | 0.033 | 1.04 | 2.48 | 1.36 | 0.225 | 0.83 | 2.22 |
Lobular or ductal histology vs. other | 1.37 | 0.152 | 0.89 | 2.10 | ||||
Chemotherapy vs. no | 2.24 | 0.000 | 1.52 | 3.31 | 1.06 | 0.817 | 0.65 | 1.74 |
Radiotherapy vs. no | 1.29 | 0.61 | 0.47 | 3.52 |
Variable | Low Risk < 500 | High Risk > 500 | p-Value | ||
---|---|---|---|---|---|
N = 804 | % | N = 233 | % | ||
Mean age at tumor diagnosis (years) | 62.3 (6.7) | 65.4 (9.1) | <10−6 | ||
pT | |||||
0–1 | 739 | 91.9 | 91 | 39 | <10−6 |
2–3 | 65 | 8.1 | 142 | 60.9 | |
pN | |||||
N0 | 710 | 88.3 | 72 | 30.9 | <10−6 |
N1 | 90 | 11.2 | 103 | 44.2 | |
N2 | 4 | 0.5 | 47 | 20.2 | |
N3 | 0 | - | 11 | 4.7 | |
Micrometastasis | |||||
Yes | 64 | 8 | 23 | 9.9 | 0.354 |
No | 740 | 92 | 210 | 90.1 | |
Estrogen receptor | |||||
Positive | 800 | 99.5 | 232 | 99.6 | 0.895 |
Negative | 4 | 0.5 | 1 | 0.4 | |
Progesterone receptor | |||||
Positive | 625 | 77.7 | 183 | 78.5 | 0.794 |
Negative | 179 | 22.3 | 50 | 21.4 | |
HER2 status | |||||
Positive | 41 | 5.1 | 24 | 10.3 | 0.004 |
Negative | 730 | 90.8 | 199 | 85.4 | |
Histology | |||||
Invasive lobular carcinoma | 126 | 15.7 | 55 | 23.6 | 0.023 |
Invasive ductal carcinoma | 620 | 77.1 | 169 | 72.5 | |
Mix | 20 | 4.5 | 6 | 2.6 | |
Other | 38 | 4.7 | 3 | 1.3 | |
Tumor grade | |||||
I | 312 | 38.8 | 13 | 5.6 | <10−6 |
II | 445 | 55.3 | 135 | 57.9 | |
III | 47 | 5.8 | 85 | 36.5 | |
Tubule formation | |||||
1 | 123 | 15.3 | 3 | 1.3 | <10−6 |
2 | 266 | 33.1 | 65 | 27.9 | |
3 | 415 | 51.6 | 163 | 70 | |
Nuclear pleomorphism | |||||
1 | 14 | 1.7 | 0 | 0 | <10−6 |
2 | 611 | 76 | 122 | 52.4 | |
3 | 179 | 22.3 | 110 | 47.2 | |
Mitotic activity | |||||
1 | 716 | 89.1 | 85 | 36.5 | <10−6 |
2 | 63 | 7.8 | 95 | 40.8 | |
3 | 25 | 3.1 | 53 | 22.7 | |
Emboli | |||||
Yea | 77 | 9.6 | 72 | 30.9 | <10−6 |
No | 722 | 89.8 | 160 | 68.7 | |
Surgery | |||||
Radical | 165 | 20.5 | 109 | 46.8 | <10−6 |
Conservative | 639 | 79.5 | 124 | 53.2 | |
Adjuvant chemotherapy | |||||
No | 579 | 72 | 41 | 17.6 | <10−6 |
Yes | 225 | 28 | 192 | 82.4 |
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Moreau-Bachelard, C.; Campion, L.; Robert, M.; Kerdraon, O.; Renaudeau, C.; Aumont, M.; Classe, J.-M.; Campone, M.; Frénel, J.-S. Development of a Prognostic Tool to Guide the Decision to Extend Adjuvant Aromatase Inhibitors for up to Ten Years in Postmenopausal Early Breast Cancer Patients. Cancers 2020, 12, 3725. https://doi.org/10.3390/cancers12123725
Moreau-Bachelard C, Campion L, Robert M, Kerdraon O, Renaudeau C, Aumont M, Classe J-M, Campone M, Frénel J-S. Development of a Prognostic Tool to Guide the Decision to Extend Adjuvant Aromatase Inhibitors for up to Ten Years in Postmenopausal Early Breast Cancer Patients. Cancers. 2020; 12(12):3725. https://doi.org/10.3390/cancers12123725
Chicago/Turabian StyleMoreau-Bachelard, Camille, Loïc Campion, Marie Robert, Olivier Kerdraon, Céline Renaudeau, Maud Aumont, Jean-Marc Classe, Mario Campone, and Jean-Sébastien Frénel. 2020. "Development of a Prognostic Tool to Guide the Decision to Extend Adjuvant Aromatase Inhibitors for up to Ten Years in Postmenopausal Early Breast Cancer Patients" Cancers 12, no. 12: 3725. https://doi.org/10.3390/cancers12123725