The Role of Post-Mastectomy Radiotherapy in T1-2N1 Breast Cancer Patients: Propensity Score Matched Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Treatment
2.3. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Treatment Outcomes
3.3. Treatment Outcomes According to Prognostic Factors
3.4. Treatment Outcomes According to the Use of PMRT
3.5. RT-Related Toxicities
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Poortmans, P.M.; Weltens, C.; Fortpied, C.; Kirkove, C.; Peignaux-Casasnovas, K.; Budach, V.; van der Leij, F.; Vonk, E.; Weidner, N.; Rivera, S.; et al. Internal mammary and medial supraclavicular lymph node chain irradiation in stage I-III breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial. Lancet Oncol. 2020, 21, 1602–1610. [Google Scholar] [CrossRef]
- McGale, P.; Taylor, C.; Correa, C.; Cutter, D.; Duane, F.; Ewertz, M.; Gray, R.; Mannu, G.; Peto, R.; Whelan, T.; et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014, 383, 2127–2135. [Google Scholar] [PubMed]
- National Comprehensive Cancer Network Breast Cancer (Version 4. 2023). Available online: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf (accessed on 24 March 2023).
- Henderson, I.C.; Berry, D.A.; Demetri, G.D.; Cirrincione, C.T.; Goldstein, L.J.; Martino, S.; Ingle, J.N.; Cooper, M.R.; Hayes, D.F.; Tkaczuk, K.H.; et al. Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J. Clin. Oncol. 2003, 21, 976–983. [Google Scholar] [CrossRef]
- Jang, B.S.; Shin, K.H. Postmastectomy Radiation Therapy in Patients With Minimally Involved Lymph Nodes: A Review of the Current Data and Future Directions. J. Breast Cancer 2022, 25, 1–12. [Google Scholar] [CrossRef]
- Piccart-Gebhart, M.J.; Procter, M.; Leyland-Jones, B.; Goldhirsch, A.; Untch, M.; Smith, I.; Gianni, L.; Baselga, J.; Bell, R.; Jackisch, C.; et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 2005, 353, 1659–1672. [Google Scholar] [CrossRef] [PubMed]
- von Minckwitz, G.; Procter, M.; de Azambuja, E.; Zardavas, D.; Benyunes, M.; Viale, G.; Suter, T.; Arahmani, A.; Rouchet, N.; Clark, E.; et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N. Engl. J. Med. 2017, 377, 122–131. [Google Scholar] [CrossRef]
- Curigliano, G.; Burstein, H.J.; Winer, E.P.; Gnant, M.; Dubsky, P.; Loibl, S.; Colleoni, M.; Regan, M.M.; Piccart-Gebhart, M.; Senn, H.J.; et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann. Oncol. 2017, 28, 1700–1712. [Google Scholar] [CrossRef]
- Recht, A.; Comen, E.A.; Fine, R.E.; Fleming, G.F.; Hardenbergh, P.H.; Ho, A.Y.; Hudis, C.A.; Hwang, E.S.; Kirshner, J.J.; Morrow, M.; et al. Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update. Pract. Radiat. Oncol. 2016, 6, e219–e234. [Google Scholar] [CrossRef] [PubMed]
- Aristei, C.; Kaidar-Person, O.; Boersma, L.; Leonardi, M.C.; Offersen, B.; Franco, P.; Arenas, M.; Bourgier, C.; Pfeffer, R.; Kouloulias, V.; et al. The 2022 Assisi Think Tank Meeting: White paper on optimising radiation therapy for breast cancer. Crit. Rev. Oncol. Hematol. 2023, 187, 104035. [Google Scholar] [CrossRef]
- Whelan, T.J.; Olivotto, I.A.; Parulekar, W.R.; Ackerman, I.; Chua, B.H.; Nabid, A.; Vallis, K.A.; White, J.R.; Rousseau, P.; Fortin, A.; et al. Regional Nodal Irradiation in Early-Stage Breast Cancer. N. Engl. J. Med. 2015, 373, 307–316. [Google Scholar] [CrossRef]
- Senkus, E.; Cardoso, M.J.; Kaidar-Person, O.; Lacko, A.; Meattini, I.; Poortmans, P. De-escalation of axillary irradiation for early breast cancer—Has the time come? Cancer Treat. Rev. 2021, 101, 102297. [Google Scholar] [CrossRef] [PubMed]
- Hennequin, C.; Bossard, N.; Servagi-Vernat, S.; Maingon, P.; Dubois, J.B.; Datchary, J.; Carrie, C.; Roullet, B.; Suchaud, J.P.; Teissier, E.; et al. Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy. Int. J. Radiat. Oncol. Biol. Phys. 2013, 86, 860–866. [Google Scholar] [CrossRef]
- Yu, J.I.; Park, W.; Choi, D.H.; Huh, S.J.; Nam, S.J.; Kim, S.W.; Lee, J.E.; Kil, W.H.; Im, Y.H.; Ahn, J.S.; et al. Prognostic Modeling in Pathologic N1 Breast Cancer Without Elective Nodal Irradiation After Current Standard Systemic Management. Clin. Breast Cancer 2015, 15, e197–e204. [Google Scholar] [CrossRef] [PubMed]
- McBride, A.; Allen, P.; Woodward, W.; Kim, M.; Kuerer, H.M.; Drinka, E.K.; Sahin, A.; Strom, E.A.; Buzdar, A.; Valero, V.; et al. Locoregional recurrence risk for patients with T1,2 breast cancer with 1-3 positive lymph nodes treated with mastectomy and systemic treatment. Int. J. Radiat. Oncol. Biol. Phys. 2014, 89, 392–398. [Google Scholar] [CrossRef] [PubMed]
- Bazan, J.G.; Majithia, L.; Quick, A.M.; Wobb, J.L.; Terando, A.M.; Agnese, D.M.; Farrar, W.; White, J.R. Heterogeneity in Outcomes of Pathologic T1-2N1 Breast Cancer After Mastectomy: Looking Beyond Locoregional Failure Rates. Ann. Surg. Oncol. 2018, 25, 2288–2295. [Google Scholar] [CrossRef]
- Macdonald, S.M.; Abi-Raad, R.F.; Alm El-Din, M.A.; Niemierko, A.; Kobayashi, W.; McGrath, J.J.; Goldberg, S.I.; Powell, S.; Smith, B.; Taghian, A.G. Chest wall radiotherapy: Middle ground for treatment of patients with one to three positive lymph nodes after mastectomy. Int. J. Radiat. Oncol. Biol. Phys. 2009, 75, 1297–1303. [Google Scholar] [CrossRef]
- Tendulkar, R.D.; Rehman, S.; Shukla, M.E.; Reddy, C.A.; Moore, H.; Budd, G.T.; Dietz, J.; Crowe, J.P.; Macklis, R. Impact of postmastectomy radiation on locoregional recurrence in breast cancer patients with 1-3 positive lymph nodes treated with modern systemic therapy. Int. J. Radiat. Oncol. Biol. Phys. 2012, 83, e577–e581. [Google Scholar] [CrossRef]
- Morrow, M.; Van Zee, K.J.; Patil, S.; Petruolo, O.; Mamtani, A.; Barrio, A.V.; Capko, D.; El-Tamer, M.; Gemignani, M.L.; Heerdt, A.S.; et al. Axillary Dissection and Nodal Irradiation Can Be Avoided for Most Node-positive Z0011-eligible Breast Cancers: A Prospective Validation Study of 793 Patients. Ann. Surg. 2017, 266, 457–462. [Google Scholar] [CrossRef] [PubMed]
- Zeidan, Y.H.; Habib, J.G.; Ameye, L.; Paesmans, M.; de Azambuja, E.; Gelber, R.D.; Campbell, I.; Nordenskjold, B.; Gutierez, J.; Anderson, M.; et al. Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial. Int. J. Radiat. Oncol. Biol. Phys. 2018, 101, 316–324. [Google Scholar] [CrossRef] [PubMed]
- Overgaard, M.; Nielsen, H.M.; Overgaard, J. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials. Radiother. Oncol. 2007, 82, 247–253. [Google Scholar]
- Park, H.J.; Shin, K.H.; Kim, J.H.; Ahn, S.D.; Kim, J.Y.; Park, W.; Kim, Y.B.; Kim, Y.J.; Kim, J.H.; Kim, K.; et al. Incorporating Risk Factors to Identify the Indication of Post-mastectomy Radiotherapy in N1 Breast Cancer Treated with Optimal Systemic Therapy: A Multicenter Analysis in Korea (KROG 14-23). Cancer Res. Treat. 2017, 49, 739–747. [Google Scholar] [CrossRef]
- Byun, H.K.; Chang, J.S.; Im, S.H.; Kirova, Y.M.; Arsene-Henry, A.; Choi, S.H.; Cho, Y.U.; Park, H.S.; Kim, J.Y.; Suh, C.O.; et al. Risk of Lymphedema Following Contemporary Treatment for Breast Cancer: An Analysis of 7617 Consecutive Patients From a Multidisciplinary Perspective. Ann. Surg. 2021, 274, 170–178. [Google Scholar] [CrossRef]
- Nos, C.; Clough, K.B.; Bonnier, P.; Lasry, S.; Le Bouedec, G.; Flipo, B.; Classe, J.M.; Missana, M.C.; Doridot, V.; Giard, S.; et al. Upper outer boundaries of the axillary dissection. Result of the SENTIBRAS protocol: Multicentric protocol using axillary reverse mapping in breast cancer patients requiring axillary dissection. Eur. J. Surg. Oncol. 2016, 42, 1827–1833. [Google Scholar] [CrossRef]
- Gross, J.P.; Sachdev, S.; Helenowski, I.B.; Lipps, D.; Hayes, J.P.; Donnelly, E.D.; Strauss, J.B. Radiation Therapy Field Design and Lymphedema Risk After Regional Nodal Irradiation for Breast Cancer. Int. J. Radiat. Oncol. Biol. Phys. 2018, 102, 71–78. [Google Scholar] [CrossRef]
- Hernandez, M.; Zhang, R.; Sanders, M.; Newhauser, W. A treatment planning comparison of volumetric modulated arc therapy and proton therapy for a sample of breast cancer patients treated with post-mastectomy radiotherapy. J. Proton Ther. 2015, 1, 119. [Google Scholar] [CrossRef] [PubMed]
- Depauw, N.; Batin, E.; Daartz, J.; Rosenfeld, A.; Adams, J.; Kooy, H.; MacDonald, S.; Lu, H.M. A novel approach to postmastectomy radiation therapy using scanned proton beams. Int. J. Radiat. Oncol. Biol. Phys. 2015, 91, 427–434. [Google Scholar] [CrossRef]
- Burstein, H.J.; Bellon, J.R.; Galper, S.; Lu, H.M.; Kuter, I.; Taghian, A.G.; Wong, J.; Gelman, R.; Bunnell, C.A.; Parker, L.M.; et al. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 2006, 64, 496–504. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Becciolini, A.; Biggeri, A.; Pacini, P.; Muirhead, C.R. Second malignancies in breast cancer patients following radiotherapy: A study in Florence, Italy. Breast Cancer Res. 2011, 13, R38. [Google Scholar] [CrossRef] [PubMed]
- Darby, S.C.; Ewertz, M.; McGale, P.; Bennet, A.M.; Blom-Goldman, U.; Bronnum, D.; Correa, C.; Cutter, D.; Gagliardi, G.; Gigante, B.; et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N. Engl. J. Med. 2013, 368, 987–998. [Google Scholar] [CrossRef]
Total (n = 504) | Before PSM | After PSM | |||||
---|---|---|---|---|---|---|---|
Non-PMRT (n = 433) | PMRT (n = 71) | p | Non-PMRT (n = 142) | PMRT (n = 71) | p | ||
Age (years, range) | Median 49.0 (24–84) | Median 48 (32–74) | Median 49 (24–84) | Median 48 (32–74) | Median 48 (31–80) | ||
Menopause | 0.395 | 0.766 | |||||
Pre- | 289 (57.3) | 245 (56.6) | 44 (62.0) | 85 (59.9) | 44 (62.0) | ||
Post- | 215 (42.7) | 188 (43.4) | 27 (38.0) | 57 (40.1) | 27 (38.0) | ||
Laterality | 0.841 | 0.771 | |||||
Rt. | 250 (49.6) | 214 (49.4) | 36 (50.7) | 67 (47.2) | 36 (50.7) | ||
Lt | 254 (50.4) | 219 (50.6) | 35 (49.3) | 75 (52.8) | 35 (49.3) | ||
Location | 0.448 | 0.530 | |||||
Laterally confined | 169 (33.5) | 146 (33.7) | 23 (32.4) | 55 (38.7) | 23 (32.4) | ||
Inner/central | 139 (27.6) | 123 (28.4) | 16 (22.5) | 34 (23.9) | 16 (22.5) | ||
Multicentric | 196 (38.9) | 164 (37.9) | 32 (45.1) | 53 (37.3) | 32 (45.1) | ||
Multifocality | 0.042 | 0.114 | |||||
No | 317 (62.9) | 280 (64.7) | 37 (52.1) | 90 (63.4) | 37 (52.1) | ||
Yes | 187 (37.1) | 153 (35.3) | 34 (47.9) | 52 (36.7) | 34 (47.9) | ||
Pathology | 0.457 | 0.124 | |||||
IDC | 456 (90.5) | 394 (91.0) | 62 (87.3) | 134 (94.4) | 62 (87.3) | ||
ILC | 21 (4.2) | 18 (4.2) | 3 (4.2) | 4 (2.8) | 3 (4.2) | ||
Others | 27 (5.3) | 21 (4.8) | 6 (8.5) | 4 (2.8) | 6 (8.5) | ||
Grade | 0.026 | 0.282 | |||||
Low | 77 (15.3) | 73 (16.9) | 4 (5.6) | 31 (21.8) | 4 (5.6) | ||
Intermediate | 262 (52.0) | 225 (52.0) | 37 (52.1) | 62 (43.7) | 37 (52.1) | ||
High | 165 (32.7) | 135 (31.2) | 30 (42.3) | 49 (34.5) | 30 (42.3) | ||
LVI | <0.001 | 0.831 | |||||
Negative | 244 (48.4) | 224 (51.7) | 20 (28.2) | 42 (29.6) | 20 (28.2) | ||
Positive | 260 (51.6) | 209 (48.3) | 51 (71.8) | 100 (70.4) | 51 (71.8) | ||
Ki-67 | 0.858 | 0.43 | |||||
1+/2+ | 406 (80.6) | 350 (80.8) | 56 (78.9) | 105 (73.9) | 56 (78.9) | ||
3+/4+ | 98 (19.4) | 83 (19.2) | 15 (21.1) | 37 (26.1) | 15 (21.1) | ||
ER | 0.152 | 0.452 | |||||
Negative | 111 (22.0) | 100 (23.1) | 11 (15.5) | 28 (19.7) | 11 (15.5) | ||
Positive | 393 (78.0) | 333 (76.9) | 60 (84.5) | 114 (80.3) | 60 (84.5) | ||
HER2 status | 0.82 | 0.586 | |||||
Negative | 360 (71.4) | 310 (71.6) | 50 (70.4) | 105 (73.9) | 50 (70.4) | ||
Positive | 142 (28.2) | 121 (27.9) | 21 (29.6) | 37 (26.1) | 21 (29.6) | ||
Unknown | 2 (0.4) | 2 (0.5) | 0 (0.0) | 0 | 0 (0.0) | ||
Subtype | 0.463 | 0.492 | |||||
HR+ | 391 (77.6) | 331 (76.4) | 60 (84.5) | 114 (80.3) | 60 (84.5) | ||
HER2+ | 64 (12.7) | 57 (13.2) | 7 (9.9) | 13 (9.2) | 7 (9.9) | ||
TNBC | 47 (9.3) | 43 (9.9) | 4 (5.6) | 15 (10.6) | 4 (5.6) | ||
Unclassified | 2 (0.4) | 2 (4.6) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
T stage | 0.009 | 0.911 | |||||
T1 | 199 (39.5) | 181 (41.8) | 18 (25.4) | 35 (24.6) | 18 (25.4) | ||
T2 | 305 (60.5) | 252 (58.2) | 53 (74.6) | 107 (75.4) | 53 (74.6) | ||
Number of dissected LNs | 19 (1~44) | 18 (1~43) | 21 (3~44) | 0.063 | 20 (9~37) | 21 (3~44) | 0.622 |
Number of LN metastases | <0.001 | 0.282 | |||||
1 | 288 (57.1) | 276 (63.7) | 12 (16.9) | 31 (21.8) | 12 (16.9) | ||
2 | 136 (27.0) | 107 (24.7) | 29 (40.8) | 62 (43.7) | 29 (40.8) | ||
3 | 80 (15.9) | 50 (11.5) | 30 (42.3) | 49 (34.5) | 30 (42.3) | ||
RM | 0.784 | 0.426 | |||||
Negative | 445 (88.3) | 383 (88.5) | 62 (87.3) | 129 (90.8) | 62 (87.3) | ||
Close | 59 (11.7) | 50 (11.5) | 9 (12.7) | 13 (9.2) | 9 (12.7) | ||
Axillary management | 0.031 | 0.497 | |||||
SLNB | 79 (15.7) | 74 (17.1) | 5 (7.0) | 14 (9.9) | 5 (7.0) | ||
ALND | 425 (84.3) | 359 (82.9) | 66 (93.0) | 128 (90.1) | 66 (93.0) | ||
Adjuvant therapy | |||||||
Anthracycline | 426 (84.5) | 364 (84.1) | 62 (87.3) | 0.482 | 129 (90.8) | 62 (87.3) | 0.426 |
Taxane | 432 (85.7) | 364 (84.1) | 68 (95.8) | 0.009 | 136 (95.8) | 68 (95.8) | 1 |
Anti-HER2 | 127 (25.2) | 107 (24.7) | 20 (28.2) | 0.607 | 37 (26.1) | 20 (28.2) | 0.743 |
Endocrine | 393 (78.0) | 332 (76.7) | 61 (85.9) | 0.082 | 117 (82.4) | 61 (85.9) | 0.513 |
Variables | LRRFS | DFS | OS | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
UVA | MVA | UVA | MVA | UVA | MVA | |||||||
p | p | HR | 95% CI | p | p | HR | 95% CI | p | p | HR | 95% CI | |
Age (yrs) | 0.771 | 0.274 | <0.001 | |||||||||
Age (≤50 vs. >50) | 0.5 | 0.308 | 0.014 | 0.716 | 1.198 | 0.453–3.172 | ||||||
Menstruation (Pre vs. Post) | 0.466 | 0.374 | 0.004 | 0.162 | 2.008 | 0.756–5.336 | ||||||
Location (Medial/multicentric vs. Laterally confined) | 0.075 | 0.056 | 0.137 | 0.018–1.050 | 0.366 | 0.614 | ||||||
Multifocality (No vs. Yes) | 0.213 | 0.268 | 0.049 | 0.103 | 0.553 | 0.271–1.127 | ||||||
Grade (Low/Int vs. High) | 0.529 | 0.123 | 0.148 | |||||||||
Subtype (HR+ vs. HER2 +) | 0.399 | 0.053 | 0.112 | 0.298 | 0.105–1.124 | 0.983 | ||||||
Subtype (HR+ vs. TNBC) | 0.162 | 0.963 | 0.108 | |||||||||
pT stage (1 vs. 2) | 0.159 | 0.118 | 0.026 | 0.076 | 1.869 | 0.936–3.732 | ||||||
Number of LN metastasis (1, 2 vs. 3) | 0.010 | 0.005 | 4.619 | 1.6–13.338 | 0.014 | 0.02 | 2.1 | 1.126–3.917 | 0.099 | 0.261 | 1.489 | 0.743–2.982 |
Extranodal extension (No vs. Yes) | 0.897 | 0.138 | 0.574 | |||||||||
LVI (No vs. Yes) | 0.333 | 0.098 | 0.132 | 1.555 | 0.875–2.761 | 0.013 | 0.023 | 2.127 | 1.112–4.070 | |||
Resection margin (Negative vs. Close) | 0.267 | 0.334 | 0.911 |
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Kim, K.; Park, W.; Kim, H.; Cho, W.K.; Kim, N.; Nam, S.J.; Kim, S.W.; Lee, J.E.; Yu, J.; Chae, B.J.; et al. The Role of Post-Mastectomy Radiotherapy in T1-2N1 Breast Cancer Patients: Propensity Score Matched Analysis. Cancers 2023, 15, 5473. https://doi.org/10.3390/cancers15225473
Kim K, Park W, Kim H, Cho WK, Kim N, Nam SJ, Kim SW, Lee JE, Yu J, Chae BJ, et al. The Role of Post-Mastectomy Radiotherapy in T1-2N1 Breast Cancer Patients: Propensity Score Matched Analysis. Cancers. 2023; 15(22):5473. https://doi.org/10.3390/cancers15225473
Chicago/Turabian StyleKim, Kangpyo, Won Park, Haeyoung Kim, Won Kyung Cho, Nalee Kim, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Jonghan Yu, Byung Joo Chae, and et al. 2023. "The Role of Post-Mastectomy Radiotherapy in T1-2N1 Breast Cancer Patients: Propensity Score Matched Analysis" Cancers 15, no. 22: 5473. https://doi.org/10.3390/cancers15225473