Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep 14;15(18):4567.
doi: 10.3390/cancers15184567.

Negative Survival Impact of Occult Lymph Node Involvement in Small HER2-Positive Early Breast Cancer Treated by Up-Front Surgery

Gilles Houvenaeghel  1 , Monique Cohen  1 , Marc Martino  1 , Fabien Reyal  2 , Jean-Marc Classe  3 , Marie-Pierre Chauvet  4 , Pierre-Emmanuel Colombo  5 , Mellie Heinemann  6 , Eva Jouve  7 , Pierre Gimbergues  8 , Anne-Sophie Azuar  9 , Charles Coutant  10 , Anthony Gonçalves  11 , Alexandre de Nonneville  11
Affiliations

Negative Survival Impact of Occult Lymph Node Involvement in Small HER2-Positive Early Breast Cancer Treated by Up-Front Surgery

Gilles Houvenaeghel et al. Cancers (Basel). .

Abstract

(1) Background: The independent negative prognostic value of isolated tumor cells or micro-metastases in axillary lymph nodes has been established in triple-negative breast cancers (BC). However, the prognostic significance of pN0(i+) or pN1mi in HER2-positive BCs treated by primary surgery remains unexplored. Therefore, our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive BC patients undergoing up-front surgery on their outcomes. (2) Methods: We retrospectively analyzed 23,650 patients treated in 13 French cancer centers from 1991 to 2013. pN status was categorized as pN0, pN0(i+), pN1mi, and pNmacro. The effect of pN0(i+) or pN1mi on outcomes was investigated both in the entire cohort of patients and in pT1a-b tumors. (3) Results: Of 1771 HER2-positive BC patients included, pN status distributed as follows: 1047 pN0 (59.1%), 60 pN0(i+) (3.4%), 118 pN1mi (6.7%), and 546 pN1 macro-metastases (30.8%). pN status was significantly associated with sentinel lymph node biopsy, axillary lymph node dissection, age, ER status, tumor grade, and size, lymphovascular invasion, adjuvant systemic therapy (ACt), and radiation therapy. With 61 months median follow-up (mean 63.2; CI 95% 61.5-64.9), only pN1 with macro-metastases was independently associated with a negative impact on overall, disease-free, recurrence-free, and metastasis-free survivals in multivariate analysis. In the pT1a-b subgroup including 474 patients, RFS was significantly decreased in multivariate analysis for pT1b BC without ACt (HR 2.365, 1.04-5.36, p = 0.039) and for pN0(i+)/pN1mi patients (HR 2.518, 1.03-6.14, p = 0.042). (4) Conclusions: Survival outcomes were not adversely affected by pN0(i+) and pN1mi in patients with HER2-positive BC. However, in the case of pT1a-b HER2-positive BC, a negative impact on RFS was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without ACt. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based ACt for these patients.

Keywords: HER2-positive; breast cancer; micro-metastases; sentinel node; survival.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Recurrence-free survival adjusted on ER status, age, LVI, and tumor size between (A) patients with pT1a-b pN0 or pN0(i+)/pN1mi tumors, and (B) with or without adjuvant chemotherapy.
Figure 2
Figure 2
Recurrence-free survival according to tumor size and nodal status in pT1a-b patients.
Figure 3
Figure 3
Recurrence-free survival adjusted on LVI, ER status, age groups, pN status, and pT size in (A) patients with pT1a-b pN0 or pN0(i+)/pN1mi tumors according to adjuvant chemotherapy, and (B) in patients with pT1a-b tumors according to nodal status.
Figure 4
Figure 4
Recurrence-free survival according to adjuvant chemotherapy and nodal status in pT1a patients.
Figure 5
Figure 5
Recurrence-free survival according to adjuvant chemotherapy and nodal status in pT1b patients.
See this image and copyright information in PMC

References

    1. Madsen E.V.E., Elias S.G., van Dalen T., van Oort P.M.P., van Gorp J., Gobardhan P.D., Bongers V. Predictive factors of isolated tumor cells and micrometastases in axillary lymph nodes in breast cancer. Breast. 2013;22:748–752. doi: 10.1016/j.breast.2012.12.013. - DOI - PubMed
    1. Houvenaeghel G., Classe J.-M., Garbay J.-R., Giard S., Cohen M., Faure C., Hélène C., Belichard C., Uzan S., Hudry D., et al. Prognostic value of isolated tumor cells and micrometastases of lymph nodes in early-stage breast cancer: A French sentinel node multicenter cohort study. Breast. 2014;23:561–566. doi: 10.1016/j.breast.2014.04.004. - DOI - PubMed
    1. Andersson Y., Bergkvist L., Frisell J., de Boniface J. Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes. Breast Cancer Res. Treat. 2018;171:359–369. doi: 10.1007/s10549-018-4820-0. - DOI - PubMed
    1. Van Roozendaal L.M., Schipper R.J., Van de Vijver K.K.B.T., Haekens C.M., Lobbes M.B.I., Tjan-Heijnen V.C.G., de Boer M., Smidt M.L. The impact of the pathological lymph node status on adjuvant systemic treatment recommendations in clinically node negative breast cancer patients. Breast Cancer Res. Treat. 2014;143:469–476. doi: 10.1007/s10549-013-2822-5. - DOI - PubMed
    1. Maibenco D.C., Dombi G.W., Kau T.Y., Severson R.K. Significance of micrometastases on the survival of women with T1 breast cancer. Cancer. 2006;107:1234–1239. doi: 10.1002/cncr.22112. - DOI - PubMed