HER2-positive breast cancer necessitates at least 1 year of continuous trastuzumab treatment to achieve optimal therapeutic efficacy. Our results demonstrate that the early stage HER2-enriched breast tumor patients who receive NAT have a comparative OS to those who undergo AT. Additionally, greater local-regional control is attained in those who receive mastectomy compared to those who receive BCT before the era of trastuzumab administration; nevertheless, women with this disease who receive trastuzumab treatment derive an equivalent LRR rate with the two surgical approaches.
In agreement with our results, some trials ascertain no differences between patients with early HER2-positive breast cancer following treatment with NAT compared to AT in the local relapse-free survival, event-free survival, relapse-free survival as well as breast cancer-specific survival.24–26 However, the study of Chatterjee et al24 indicated that the DFS of patients in AT cohort was significantly longer than that in NAT cohort. Trastuzumab emtansine (T-DM1) is an antibody-cytotoxic drug conjugate of trastuzumab and the cytotoxic agent emtansine; it has efficacious antitumor effects in trastuzumab-sensitive and trastuzumab-resistant HER2-amplified breast tumors and was initially approved for advanced HER2-positive breast cancer patients who have previously received trastuzumab treatment.27,28 The articles of Hurvitz29 and Minckwitz,28 respectively, assessed the tumor response and the survival prognosis of early stage HER2-enriched subtype of breast tumors after treatment with T-DM1 and trastuzumab. Their findings demonstrated that women with this disease subset who received T-DM1 had significantly superior DFS and distant relapse-free survival and reduced pathological complete response (pCR) rates compared to those who received trastuzumab, but the OS was not significantly different. The mechanisms of action of T-DM1 eradicating HER2-positive breast tumor foci contrast to those of trastuzumab. T-DM1 activates caspase-3/caspase-7 to induce apoptotic cell death and releases the intracellular enzyme adenylate kinase which contributes to the cellular lysis. Trastuzumab antagonizes the constitutive growth-signaling properties of the HER2 system, mobilizes immune cells to kill the tumor target, and reinforces chemotherapy-induced cytotoxicity.27,30
For breast cancer patients with the HER2-enriched subtype, there are two distinct eras determined by the usage of trastuzumab in the adjuvant setting. In the period preceding the use of anti-HER2 targeted therapy, the LRR rate of this tumor ranges from 4% to 15%.16,31 The natural process of this phenotype of breast cancer has been positively influenced by trastuzumab.32 Yin et al33 analyzed six relevant studies and indicated that trastuzumab reduced the LRR rate of HER2-positive breast cancer by 50%. This conclusion was supported by a retrospective study performed by Panoff and colleagues,34 which found that the LRR rate of women with this disease who underwent mastectomy plus trastuzumab was 1.7%. Our article finds the different LRR rates between HER2-amplified breast tumors undergoing mastectomy and those undergoing BCT before the application of trastuzumab coupled with the identical LRR rate among both surgical scenarios after its administration, which mirrors the trastuzumab-adjusted alteration of the natural course of this disease.
There is a viewpoint suggesting that the prognosis of HER2-enriched breast cancers primarily depends on the biological characteristics of the disease rather than the content of surgical approach.35 Nevertheless, it may be somewhat confined and not comprehensive. A study enrolled 618 breast cancer patients that underwent either BCT or mastectomy, 92 of whom were classified as the HER2 subtype.21 In the BCT cohort, HER2 subtype of breast cancer and lymph node positivity were independent prognostic factors associated with high-risk of LRR. This cancer subset was not associated with increased risk of LRR in the mastectomy cohort. Similarly, our results reaffirm that the different extents of surgery may be related to the prognosis of HER2-overexpression breast carcinoma devoid of trastuzumab treatment.
There are some limitations of this article that deserve mention. First, despite the absence of publication bias, only English literature was included which might give rise to selection bias. Second, the included studies in partial meta-analyses were limited, which might lead to result bias. More importantly, we did not investigate other factors that might affect the outcome of LRR in women because of insufficient information provided by the publications, such as chemotherapy regimen, fractionated mode, and dose of radiotherapy.
The OS of HER2-amplified breast tumor patients treated with NAT is equivalent to those with AT treatment. The LRR rate of those women who undergo mastectomy compared to BCT is identical in the absence of trastuzumab treatment, but mastectomy reduces the LRR rate compared to BCT in women who receive trastuzumab treatment.
Ethics approval and consent to participate
This article does not contain any studies with human participants or animals performed by any of the authors.
The authors report no conflicts of interest in this work.
Lin He,1,* Qian Wu,1,* Jing Xiong,2 Zhumin Su,3 Biyuan Zhang,4 Yuhua Song1
1Breast Center B Ward, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China; 2Department of Geriatrics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China; 3Department of Neurology, The People’s Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 4Department of Radiotherapy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China
Correspondence: Yuhua Song
Breast Center B ward, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao, Shandong Province, People’s Republic of China
Tel +86 1 369 869 1275
Email [email protected]
*These authors contributed equally to this work
1. Clough KB, Acosta-Marin V, Nos C, et al. Rates of neoadjuvant chemotherapy and oncoplastic surgery for breast cancer surgery: a french national survey. Ann Surg Oncol. 2015;22(11):3504–3511. doi:10.1245/s10434-015-4378-6
2. Mougalian SS, Soulos PR, Killelea BK, et al. Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer. 2015;121(15):2544–2552. doi:10.1002/cncr.29348
3. Vugts G, Maaskant-Braat AJ, Nieuwenhuijzen GA, Roumen RM, Luiten EJ, Voogd AC. Patterns of care in the administration of neo-adjuvant chemotherapy for breast cancer. A population-based study. Breast J. 2016;22(3):316–321. doi:10.1111/tbj.12568
4. Peto R, Davies C, Godwin J, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379(9814):432–444. doi:10.1016/S0140-6736(11)61625-5
5. Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16(8):2672–2685. doi:10.1200/JCO.1922.214.171.12472
6. Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26(5):778–785. doi:10.1200/JCO.2007.15.0235
7. van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19(22):4224–4237. doi:10.1200/JCO.2001.19.22.4224
8. Early Breast Cancer Trialist’ Collaborative Group (EBCTG); Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27–39. doi:10.1016/S1470-2045(17)30777-5
9. Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005;97(3):188–194. doi:10.1093/jnci/dji021
10. Fisher B, Bauer M, Margolese R, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med. 1985;312(11):665–673. doi:10.1056/NEJM198503143121101
11. Veronesi U, Saccozzi R, Del Vecchio M, et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med. 1981;305(1):6–11. doi:10.1056/NEJM198107023050102
12. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366(9503):2087–2106. doi:10.1016/S0140-6736(05)67887-7
13. CC N. Treatment of early breast cancer. JAMA. 1991;265:391–395.
14. Buchholz TA. Radiation therapy for early-stage breast cancer after breast-conserving surgery. N Engl J Med. 2009;360(1):63–70. doi:10.1056/NEJMct0803525
15. Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med. 2014;138(2):241–256. doi:10.5858/arpa.2013-0953-SA
16. Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 2010;28(10):1684–1691. doi:10.1200/JCO.2009.24.9284
17. Debled M, MacGrogan G, Breton-Callu C, et al. Surgery following neoadjuvant chemotherapy for HER2-positive locally advanced breast cancer. Time to reconsider the standard attitude. Eur j cancer. 2015;51(6):697–704. doi:10.1016/j.ejca.2015.01.063
18. Stewart LA, Clarke M, Rovers M, et al. Preferred reporting items for systematic review and meta-analyses of individual participant data: the PRISMA-IPD statement. JAMA. 2015;313(16):1657–1665. doi:10.1001/jama.2015.3656
19. Sutton AJ, Abrams KR, Jones DR. Methods for Meta-analysis in Medical Research. Wiley Series in Probability and Statistics-applied Probability and Statistics Section. Hoboken: Wiley; 2008.
20. Ihemelandu CU, Naab TJ, Mezghebe HM, et al. Treatment and survival outcome for molecular breast cancer subtypes in black women. Ann Surg. 2008;247(3):463–469. doi:10.1097/SLA.0b013e31815d744a
21. Gabos Z, Thoms J, Ghosh S, et al. The association between biological subtype and locoregional recurrence in newly diagnosed breast cancer. Breast Cancer Res Treat. 2010;124(1):187–194. doi:10.1007/s10549-010-1135-1
22. Herrero-Vicent C, Guerrero-Zotano A, Gavila-Gregori J, et al. A prognostic index for locoregional recurrence after neoadjuvant chemotherapy. Ecancermedicalscience. 2016;10:647. doi:10.3332/ecancer.2016.647
23. Straver ME, Rutgers EJ, Rodenhuis S, et al. The relevance of breast cancer subtypes in the outcome of neoadjuvant chemotherapy. Ann Surg Oncol. 2010;17(9):2411–2418. doi:10.1245/s10434-010-1008-1
24. Chatterjee S, Arunsingh M, Agrawal S, et al. Outcomes following a moderately hypofractionated adjuvant radiation (START B Type) schedule for breast cancer in an unscreened non-caucasian population. Clin Oncol (R Coll Radiol). 2016;28(10):e165–e172. doi:10.1016/j.clon.2016.05.008
25. Gonzalez-Angulo AM, Parinyanitikul N, Lei X, et al. Effect of adjuvant trastuzumab among patients treated with anti-HER2-based neoadjuvant therapy. Br J Cancer. 2015;112(4):630–635. doi:10.1038/bjc.2014.647
26. Palmieri C, Macpherson IR, Yan K, et al. Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer. Oncotarget. 2016;7(11):13209–13220. doi:10.18632/oncotarget.4801
27. Lewis Phillips GD, Li G, Dugger DL, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008;68(22):9280–9290. doi:10.1158/0008-5472.CAN-08-1776
28. von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617–628. doi:10.1056/NEJMoa1814017
29. Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115–126. doi:10.1016/S1470-2045(17)30716-7
30. Sliwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol. 1999;26(4 Suppl 12):60–70.
31. Nguyen PL, Taghian AG, Katz MS, et al. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol. 2008;26(14):2373–2378. doi:10.1200/JCO.2007.14.4287
32. Tsoutsou PG, Vozenin MC, Durham AD, Bourhis J. How could breast cancer molecular features contribute to locoregional treatment decision making? Crit Rev Oncol Hematol. 2017;110:43–48. doi:10.1016/j.critrevonc.2016.12.006
33. Yin W, Jiang Y, Shen Z, Shao Z, Lu J. Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials. PLoS One. 2011;6(6):e21030. doi:10.1371/journal.pone.0021030
34. Panoff JE, Hurley J, Takita C, et al. Risk of locoregional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post-mastectomy radiation. Breast Cancer Res Treat. 2011;128(3):899–906. doi:10.1007/s10549-011-1495-1
35. Horton JK, Jagsi R, Woodward WA, Ho A. Breast cancer biology: clinical implications for breast radiation therapy. Int J Radiat Oncol Biol Phys. 2018;100(1):23–37. doi:10.1016/j.ijrobp.2017.08.025
Source: Cancer Management and Research.
Originally published August 29, 2019.
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