DISCUSSION

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.

CONCLUSION

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.

Disclosure

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 qdsongyh@126.com


*These authors contributed equally to this work


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Source: Cancer Management and Research.
Originally published August 29, 2019.

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