Journal List > J Breast Cancer > v.22(1) > 1119189

Hamdy: Neoadjuvant Therapy Should Be the Standard of Care for Every Node Positive Breast Cancer Patient
To the Editor:
This letter addresses a very simple, yet crucial question. Can we adopt the practice of offering neoadjuvant therapy (NAT) as a rule, for every node positive breast cancer patient, in order to avoid harmful axillary dissection in those who achieve pathological complete response (pCR)?
Sentinel lymph node biopsy (SLNB), is considered to be the standard of care for node negative breast cancer, as it can save patients from the complications of axillary lymph node dissection (ALND). These complications include lymphedema, arm stiffness, and neuralgia, all of which significantly affect the patient's quality of life and raise healthcare costs. It also allows accurate axillary staging with minimal morbidity. In patients undergoing breast conserving surgery and whole breast irradiation, it is now even acceptable to omit axillary dissection, if one to two lymph nodes (LNs) are found to be positive on SLNB [1234].
Till date, according to the European Society for Medical Oncology (ESMO) guidelines for early breast cancer, there are still no definite indications for NAT in early breast cancer, except for downsizing large tumors in women with large tumor to breast ratio, desiring conservative breast surgery. Many studies have investigated the management of the axilla, in node positive breast cancer patients who received NAT. However, none of them considered node positivity to be an absolute indication for NAT. NAT is still not considered as the standard of care in early breast cancer, despite there being evidence that achieving pCR after NAT improves both, overall survival (OS), and disease free survival (DFS). The National Comprehensive Cancer Network guidelines have recently considered node positivity, which is more likely to convert to node negativity, as an indication for NAT. However, it is recommended, that a dual mapping technique is applied for sentinel lymph node (SLN) localization to remove two or more LNs, and to insert a clip in positive LNs before starting NAT in these patients [1235678].
In the setting of breast cancer, NAT (including chemotherapy, endocrine, and targeted therapy) offers the same long-term outcomes as that of adjuvant therapy [9]. However, it offers the advantages of facilitating conservative breast surgery in patients who were not suitable candidates for upfront breast conservation. It also helps in downsizing inoperable tumors to make them amenable for surgery. In addition, it provides important prognostic and therapeutic data, based on the magnitude of tumor response, especially in those who achieve pCR of the primary tumor, as well as the axillary LNs. This improves both, the OS, and the DFS. The improvement in survival is more likely to occur in triple negative breast cancer, and in human epidermal growth factor 2 (HER2)-positive breast cancer, particularly when trastuzumab is added to the treatment regimen. The patients who achieve axillary pCR, show better loco-regional and survival outcomes, irrespective of the primary tumor response [45710111213141516]. NAT also provides adequate time for genetic testing, and planning for breast reconstruction, when indicated. Furthermore, it provides information to assess the in vivo response to therapy [211].
The benefit of NAT, which is the focus of this article, lies in the opportunity to offer SLNB instead of ALND in patients with node positive breast cancer that was cleared by NAT. This consequently saves patients from the harmful outcomes of ALND [2].
The cons of NAT include both, the possibilities of over- and under-treatment. This depends on the errors in correct estimation of the extent of disease prior to, or after NAT. The possibility of disease progression during therapy also exists, particularly in chemo-resistant tumors. However, there is no significant difference in 15-year distant recurrence between NAT and adjuvant treatment. Post-NAT under-treatment can be limited by a detailed pathological assessment, meticulous tumor localization, and appropriate radiotherapy [21417].
In terms of prognosis, the response of the axillary nodes to NAT is known to be a more important factor, than the initial axillary status. The false-negative rates (FNRs) of SLNB after NAT range from 5% to 30%, but these FNRs can be reduced to less than 10% when the dual technique for SLN localization is used, and when more than two LNs can be dissected and examined [68101118192021].
At least 28% of all candidates from all breast cancer subtypes achieve pCR in both, the breast, and axillary tumor, with the highest pCR rate in hormone negative, HER2-positive breast cancer, and the lowest rate in luminal A subtype [1722]. The rates for axillary pCR are higher, reaching up to 37% (between 5% and 75%). This rate reaches up to 21% in patients with estrogen receptor-positive/HER2-negative tumors, 60% in triple negative tumors, between 67% and 73% in HER2-positive tumors when trastuzumab is used in combination with chemotherapy, and up to 97% when dual HER2 blockage is applied [7810111516202324].
Considering its significant effect on minimizing the complications and morbidities of ALND, SLNB can be considered as a goal rather than as a tool. Axillary complete pathological response can be achieved after NAT in at least 21% of luminal A, and, up to 97% of HER2-positive subtypes of node positive breast cancer. Every node positive breast cancer patient receives chemotherapy, either in the neoadjuvant or adjuvant setting. There is no significant advantage for receiving it in the adjuvant setting as compared with NAT. NAT should therefore be adopted to be the standard of care for every node positive breast cancer patient.

Notes

Conflict of Interest The author declares that they have no competing interests.

References

1. Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26:Suppl 5. v8–v30.
crossref
2. Breast cancer (version 1.2018). NCCN guidelines. National Comprehensive Cancer Network. Accessed June 2018. https://www.nccn.org/professionals/physician_gls/default.aspx#breast.
3. Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, et al. Factors affecting sentinel lymph node identification rate after neoadjuvant chemotherapy for breast cancer patients enrolled in ACOSOG Z1071 (Alliance). Ann Surg. 2015; 261:547–552.
crossref pmid pmc
4. Cook M, Johnson N. Pre-surgical chemotherapy for breast cancer may be associated with improved outcomes. Am J Surg. 2018; 215:931–934.
crossref pmid
5. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014; 384:164–172.
crossref pmid
6. Schwartz T, Fisher C. Sentinel lymph node biopsy after neoadjuvant chemotherapy for patients with axillary metastases: can we avoid the unavoidable? Ann Surg Oncol. 2016; 23:3429–3431.
crossref pmid
7. Vugts G, Maaskant-Braat AJ, de Roos WK, Voogd AC, Nieuwenhuijzen GA. Management of the axilla after neoadjuvant chemotherapy for clinically node positive breast cancer: a nationwide survey study in The Netherlands. Eur J Surg Oncol. 2016; 42:956–964.
crossref pmid
8. Mamtani A, Barrio AV, King TA, Van Zee KJ, Plitas G, Pilewskie M, et al. How often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? Results of a prospective study. Ann Surg Oncol. 2016; 23:3467–3474.
crossref pmid pmc
9. Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005; 97:188–194.
crossref pmid
10. van der Noordaa ME, van Duijnhoven FH, Straver ME, Groen EJ, Stokkel M, Loo CE, et al. Major reduction in axillary lymph node dissections after neoadjuvant systemic therapy for node-positive breast cancer by combining PET/CT and the MARI procedure. Ann Surg Oncol. 2018; 25:1512–1520.
crossref pmid
11. Diego EJ, McAuliffe PF, Soran A, McGuire KP, Johnson RR, Bonaventura M, et al. Axillary staging after neoadjuvant chemotherapy for breast cancer: a pilot study combining sentinel lymph node biopsy with radioactive seed localization of pre-treatment positive axillary lymph nodes. Ann Surg Oncol. 2016; 23:1549–1553.
crossref pmid
12. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012; 30:1796–1804.
crossref pmid
13. Hennessy BT, Hortobagyi GN, Rouzier R, Kuerer H, Sneige N, Buzdar AU, et al. Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol. 2005; 23:9304–9311.
crossref pmid
14. King TA, Morrow M. Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat Rev Clin Oncol. 2015; 12:335–343.
crossref pmid
15. Ouldamer L, Chas M, Arbion F, Body G, Cirier J, Ballester M, et al. Risk scoring system for predicting axillary response after neoadjuvant chemotherapy in initially node-positive women with breast cancer. Surg Oncol. 2018; 27:158–165.
crossref pmid
16. Boughey JC, McCall LM, Ballman KV, Mittendorf EA, Ahrendt GM, Wilke LG, et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial. Ann Surg. 2014; 260:608–614.
pmid pmc
17. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). 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; 19:27–39.
pmid pmc
18. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013; 14:609–618.
crossref pmid
19. Kang YJ, Han W, Park S, You JY, Yi HW, Park S, et al. Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy. Breast Cancer Res Treat. 2017; 166:473–480.
crossref pmid
20. Vila J, Mittendorf EA, Farante G, Bassett RL, Veronesi P, Galimberti V, et al. Nomograms for predicting axillary response to neoadjuvant chemotherapy in clinically node-positive patients with breast cancer. Ann Surg Oncol. 2016; 23:3501–3509.
crossref pmid
21. Caudle AS, Bedrosian I, Milton DR, DeSnyder SM, Kuerer HM, Hunt KK, et al. Use of sentinel lymph node dissection after neoadjuvant chemotherapy in patients with node-positive breast cancer at diagnosis: practice patterns of american society of breast surgeons members. Ann Surg Oncol. 2017; 24:2925–2934.
crossref pmid pmc
22. Swisher SK, Vila J, Tucker SL, Bedrosian I, Shaitelman SF, Litton JK, et al. Locoregional control according to breast cancer subtype and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Ann Surg Oncol. 2016; 23:749–756.
crossref pmid
23. Dominici LS, Negron Gonzalez VM, Buzdar AU, Lucci A, Mittendorf EA, Le-Petross HT, et al. Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer. Cancer. 2010; 116:2884–2889.
crossref pmid pmc
24. Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA, Black DM, Gilcrease MZ, et al. C Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection. J Clin Oncol. 2016; 34:1072–1078.
crossref pmid pmc
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Omar Hamdy
https://orcid.org/0000-0002-2924-4207

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