Cancer Res Treat.  2023 Apr;55(2):592-602. 10.4143/crt.2022.998.

Impact of Postmastectomy Radiation Therapy on Breast Cancer Patients According to Pathologic Nodal Status after Modern Neoadjuvant Chemotherapy

• Kim D
• Kim JH
• Kim IA
• Chang JH
• Shin KH

• KMID: 2541246
• DOI: http://doi.org/10.4143/crt.2022.998

Abstract

Purpose
The utility of postmastectomy radiation therapy (PMRT) for breast cancer patients after neoadjuvant chemotherapy (NAC) is highly controversial. This study evaluated the impact of PMRT according to pathologic nodal status after modern NAC.
Materials and Methods
We retrospectively reviewed 682 patients with clinical stage II-III breast cancer who underwent NAC and mastectomy from 2013 to 2017. In total, 596 patients (87.4%) received PMRT, and 86 (12.6%) did not. We investigated the relationships among locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS), and various prognostic factors. Subgroup analyses were also performed to identify patients who may benefit from PMRT.
Results
The median follow-up duration was 67 months. In ypN+ patients (n=368, 51.2%), PMRT showed significant benefits in terms of LRRFS, DFS, and OS (all p < 0.001). In multivariate analyses, histologic grade (HG) III (p=0.002), lymphovascular invasion (LVI) (p=0.045), and ypN2-3 (p=0.02) were significant risk factors for poor LRRFS. In ypN1 patients with more than two prognostic factors among luminal/human epidermal growth factor receptor-2–negative subtype, HG I-II, and absence of LVI, PMRT had no significant effect on LRRFS (p=0.18). In ypN0 patients (n=351, 48.8%), PMRT was not significantly associated with LRRFS, DFS, or OS. However, PMRT showed better LRRFS in triple-negative breast cancer (TNBC) patients (p=0.03).
Conclusion
PMRT had a major impact on treatment outcomes in patients with residual lymph nodes following NAC and mastectomy. Among ypN0 patients, PMRT may be beneficial only for those with TNBC.

Keyword

Breast neoplasms; Neoadjuvant therapy; Postmastectomy radiation therapy; Pathologic nodal stage

Figure

• 

  Fig. 1 Subgroup analyses of LRRFS according to the use of PMRT in ypN0 patients. ALND, axillary lymph node dissection; HER2, human epidermal growth factor receptor; LRRFS, locoregional recurrence-free survival; NA, not available; PMRT, postnastectomy radiation therapy; RT, radiation therapy; SLNB, sentinel lymph node biopsy. a)Significant p-value.

• 

  Fig. 2 Subgroup analyses of LRRFS according to the use of PMRT in ypN+ patients. ALND, axillary lymph node dissection; HER2, human epidermal growth factor receptor; LRRFS, locoregional recurrence-free survival; NA, not available; PMRT, postmastectomy radiation therapy; RT, radiation therapy; SLNB, sentinel lymph node biopsy. a)Significant p-value.

• 

  Fig. 3 Locoregional recurrence-free survival curves of low- (A) and high-risk (B) ypN1 patients according to postmastectomy radiation therapy (PMRT).

Reference

References

1. Gralow JR, Burstein HJ, Wood W, Hortobagyi GN, Gianni L, von Minckwitz G, et al. Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol. 2008; 26:814–9.

2. Mougalian SS, Soulos PR, Killelea BK, Lannin DR, Abu-Khalaf MM, DiGiovanna MP, et al. Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer. 2015; 121:2544–52.

3. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997; 15:2483–93.

4. Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012; 19:1508–16.

5. Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, et al. 5-Year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016; 17:791–800.

6. Sevcikova K, Vertakova-Krakovska B, Spanik S. Neoadjuvant treatment in patients with HER2-positive breast cancer. ISRN Oncol. 2013; 2013:362467.

7. Harris EE, Freilich J, Lin HY, Chuong M, Acs G. The impact of the size of nodal metastases on recurrence risk in breast cancer patients with 1–3 positive axillary nodes after mastectomy. Int J Radiat Oncol Biol Phys. 2013; 85:609–14.

8. Early Breast Cancer Trialists’ Collaborative Group, Darby S, McGale P, Correa C, Taylor C, Arriagada R, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recu-rrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011; 378:1707–16.

9. Macdonald S, Oncology R, General M. Breast cancer breast cancer. J R Soc Med. 2016; 70:515–7.

10. Zhang Y, Zhang Y, Liu Z, Qin Z, Li Y, Zhao J, et al. Impact of postmastectomy radiotherapy on locoregional control and disease-free survival in patients with breast cancer treated with neoadjuvant chemotherapy. J Oncol. 2021; 2021:6632635.

11. Ohri N, Moshier E, Ho A, Green S, Rhome R, Mazumdar M, et al. Postmastectomy radiation in breast cancer patients with pathologically positive lymph nodes after neoadjuvant chemotherapy: usage rates and survival trends. Int J Radiat Oncol Biol Phys. 2017; 99:549–59.

12. Mamounas EP, Anderson SJ, Dignam JJ, Bear HD, Julian TB, Geyer CE Jr, et al. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol. 2012; 30:3960–6.

13. Shim SJ, Park W, Huh SJ, Choi DH, Shin KH, Lee NK, et al. The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II–III breast cancer patients with pN0: a multicenter, retrospective study (KROG 12-05). Int J Radiat Oncol Biol Phys. 2014; 88:65–72.

14. Cho WK, Park W, Choi DH, Kim YB, Kim JH, Kim SS, et al. The benefit of post-mastectomy radiotherapy in ypN0 patients after neoadjuvant chemotherapy according to molecular subtypes. J Breast Cancer. 2019; 22:285–96.

15. Le Scodan R, Selz J, Stevens D, Bollet MA, de la Lande B, Daveau C, et al. Radiotherapy for stage II and stage III breast cancer patients with negative lymph nodes after preoperative chemotherapy and mastectomy. Int J Radiat Oncol Biol Phys. 2012; 82:e1–7.

16. Zhang J, Lu CY, Chen CH, Chen HM, Wu SY. Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: a cancer database analysis. Breast. 2020; 54:70–8.

17. Wang K, Jin X, Wang W, Yu X, Huang J. The role of postmastectomy radiation in patients with ypN0 breast cancer after neoadjuvant chemotherapy: a meta-analysis. BMC Cancer. 2021; 21:728.

18. Jang BS, Shin KH. 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.

19. Miyashita M, Niikura N, Kumamaru H, Miyata H, Iwamoto T, Kawai M, et al. Role of postmastectomy radiotherapy after neoadjuvant chemotherapy in breast cancer patients: a study from the Japanese Breast Cancer Registry. Ann Surg Oncol. 2019; 26:2475–85.

20. Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008; 26:778–85.

21. Haque W, Verma V, Hatch S, Suzanne Klimberg V, Brian Butler E, Teh BS. Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy. Breast Cancer Res Treat. 2018; 170:559–67.

22. Berruti A, Amoroso V, Gallo F, Bertaglia V, Simoncini E, Pedersini R, et al. Pathologic complete response as a potential surrogate for the clinical outcome in patients with breast cancer after neoadjuvant therapy: a meta-regression of 29 randomized prospective studies. J Clin Oncol. 2014; 32:3883–91.

23. Spring LM, Fell G, Arfe A, Sharma C, Greenup R, Reynolds KL, et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res. 2020; 26:2838–48.

24. Sestak I, Dowsett M, Zabaglo L, Lopez-Knowles E, Ferree S, Cowens JW, et al. Factors predicting late recurrence for estrogen receptor-positive breast cancer. J Natl Cancer Inst. 2013; 105:1504–11.

25. Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, Wesseling J, et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med. 2010; 7:e1000279.

26. Huang Z, Zhu L, Huang XB, Tang Y, Rong QL, Shi M, et al. Postmastectomy radiation therapy based on pathologic nodal status in clinical node-positive stage II to III breast cancer treated with neoadjuvant chemotherapy. Int J Radiat Oncol Biol Phys. 2020; 108:1030–9.

27. Lee J, Kim JY, Bae SJ, Cho Y, Ji JH, Kim D, et al. The impact of post-mastectomy radiotherapy on survival outcomes in breast cancer patients who underwent neoadjuvant chemotherapy. Cancers (Basel). 2021; 13:6205.

28. Wright JL, Takita C, Reis IM, Zhao W, Saigal K, Wolfson A, et al. Predictors of locoregional outcome in patients receiving neoadjuvant therapy and postmastectomy radiation. Cancer. 2013; 119:16–25.

29. Jeon SH, Shin KH, Kim JH, Kim K, Kim IA, Lee KH, et al. Effects of trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-overexpressing breast cancer patients treated with chemotherapy and radiotherapy. Breast Cancer Res Treat. 2018; 172:619–26.

30. Fowble B, Jairam AK, Wang F, Peled A, Alvarado M, Ewing C, et al. Indications for postmastectomy radiation after neoadjuvant chemotherapy in ypN0 and ypN1–3 axillary node-positive women. Clin Breast Cancer. 2018; 18:e107–13.