Metastatic mammary carcinoma despite histologically negative sentinel lymph nodes: are there any indicators for estimating recurrence and metastasis rates?

Objective: This study aimed to identify indicators for an increased frequency of recurrent or metastatic disease in women with mammary carcinoma staged negative for nodal involvement. Materials and Methods: 202/270 patients (age: mean 57.5, range 24-83 years) with histologically confirmed early stage mammary carcinoma negative for metastasis to the sentinel lymph nodes (SLN) were observed with respect to their clinical course for a mean period of 3.6 years following SLN extirpation. Results: Forty of 202 patients with negative SLN underwent chemotherapy (38/188 in the recurrence-free group vs. 2/14 in the group with progressive disease) and 79% of both subcollectives did not undergo chemotherapy. Seven of 188 of patients in the recurrence-free group received immunotherapy and none of the patients in the group with disease progression were treated with this modality. One hundred sixty-two of 202 patients with negative SLN underwent hormone therapy, 157/188 in the recurrence-free group and 5/14 in the group with disease progression. One hundred sixty-four of 202 patients with negative nodal status received adjuvant radiation therapy of the affected breast, 156/188 in the recurrence-free group and 8/14 in the group with disease progression. Conclusions: When assessing the risk profile for disease recurrence or the occurrence of metastatic disease, statistically significant differences with respect to disease progression were identified for the parameters chemo-, antibody, hormone, and radiation therapy. The preliminary observations of this study show that even those patients in an early disease stage and with negative SLNs profit from these adjuvant non-surgical therapy options.

Breast cancer; Sentinel lymph node; Recurrence and metastasis rates; Adjuvant therapy.

[1] Giammarile F., Alazraki N., Aarsvold J.N., Audisio R.A., Glass E., Grant S.F., et al.: “The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer”. Eur. J. Nucl. Med. Mol. Imaging, 2013, 40, 1932.

[2] Buscombe J., Paganelli G., Burak Z.E., Waddington W., Maublant J., Prats E., et al.: “European Association of Nuclear Medicine Oncology Committee and Dosimetry Committee. Sentinel node in breast cancer procedural guidelines”. Eur. J. Nucl. Med. Mol. Imaging, 2007, 34, 2154.

[3] Weiss M., Gildehaus F.J., Brinkbäumer K., Makowski M., Hahn K.: “Lymph kinetics with technetium-99m labeled radiopharmaceuticals- Animal studies”. Nuklearmedizin, 2005, 44, 156.

[4] Weiss M., Meyer M., Siegert S., Bartenstein P., Pfluger T.: “Metastases in patients with breast cancer despite of negative sentinel lymph node. Has the concept to be changed?” Nuklearmedizin, 2013, 52, 14.

[5] Schwartz G.F., Bartelink H., Burstein H.J.: “Adjuvant therapy in stage I carcinoma of the breast: the influence of multigene analyses and molecular phenotyping”. Breast J., 2012, 18, 303.

[6] Ahmed S.S., Thike A.A., Iqbal J., Yong W.S., Tan B., Madhukumar P., et al.: “Sentinel lymph nodes with isolated tumour cells and micrometastases in breast cancer: clinical relevance and prognostic significance”. J. Clin. Pathol., 2014, 67, 243.

[7] Berclaz B., Li S., Price K.N., Coates A.S., Castiglione-Gertsch M., Rudenstamm C.M, et al.: “Body mass index as a prognostic feature in operable breast cancer: the international breast cancer study group experience”. Ann. Oncol., 2004, 15, 875.

[8] Cserni G.: “The effect of sentinel lymph node biopsy on the Nottingham Prognostic Index in breast cancer patients”. J. R. Coll. Surg. Edinb., 2001, 46, 208.

[9] Dian D., Straub J., Scholz C., Mylonas I., Rack B., Sommer H., et al.: “Influencing factors for regional lymph node recurrence of breast cancer”. Arch. Gynecol. Obstet., 2008, 277, 127.

[10] Kwast A.B., Groothuis-Oudshoorn K.C., Grandjean I., Ho V.K., Voogd A.C., Menke-Pluymers M.B., et al.: “Histological type is not an independent prognostic factor for the risk pattern of breast cancer recurrences”. Breast Cancer Res. Treat., 2012, 135, 271.

[11] Wely van B.J., Smidt M.L., de Kievit I.M., Wauters C.A., Strobbe L.J.: “False-negative sentinel lymph node biopsy”. Br. J. Surg., 2008, 95, 1352.

[12] Dabakuyo T.S., Bonnetain F., Roignot P., Poillot M.L.: “Populationbased study of breast cancer survival in Cote d'Or: prognostic factors and relative survival”. Ann. Oncol., 2008, 19, 276.

[13] Collan Y., Eskelinen M.J., Nordling S.A.: “Prognostic studies in breast cancer. Multivariate combination of nodal status, proliferation index, tumor size and DANN ploidity”. Acta Oncol., 1994, 33, 873.

[14] Madsen E.V., Elias S.G., van Dalen T., van Oort P.M., 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.

[15] Goldhirsch A., Wood W.C., Gelber R.D.: “Progress and promise: highlight of the international expert consensus on the primary therapy of early breast cancer”. Ann. Oncol., 2007, 28, 1133.

[16] Osborne C.K., Yochmowitz M.G.: “The value of estrogen and progesterone receptors in the treatment of breast cancer”. Cancer, 1980, 46, 2884.

[17] Wang Y., Yao L., Liu Y.Q., Xu Y., Ou Y.T., Li J.F., Wang T.F.: “Different influence of Her-2 expression on the prognosis in node-positive and node-negative breast cancer”. Zhonghua Zhong Liu Za Zhi, 2010, 32, 511.

[18] Hackney L., Williams S., Bajwa S., Morley-Davies A.J., Kirby R.M., Britton I.: “Influence of tumor histology on preoperative staging accuracy of breast metastases to the axilla”. Breast J., 2013, 19, 49.

[19] Jimbo K., Kinoshita T., Suzuki J., Asaga S., Hojo T., Yoshida M., Tsuda H.: “Sentinel and nonsentinel lymph node assessment using a combination of one-step nucleic acid amplification and conventional histological examination”. Breast, 2013, 22, 1194.

[20] Gloyeske N.C., Goreal W., O'Neil M., Connor C., Tawfik O.W., Fan F.: “Outcomes of breast cancer patients with micrometastases and isolated tumor cells in sentinel lymph nodes”. In Vivo, 2011, 25, 997.

[21] Gobhardhan P.D., Elias S.G., Madsen E.V., Bongers V., Ruitenberg H.J.M., Perre C.I., van Dalen T.: “Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study”. Ann. Oncol., 2009, 20, 41.

[22] Kim H.J., Son B.H., Park E.W., Lim W.S., Seo J.Y., Jang M.A., Ku B.K.: “Axillary recurrence after negative sentinel lymph node biopsy”. Breast Cancer Res. Treat., 2009, 114, 301.

[23] Nagashima T., Sakakibara M., Nakano S., Tanabe N., Nakamura R., Nakatani Y., et al.: “Sentinel node micrometastasis and distant failure in breast cancer patients”. Breast Cancer, 2006, 13, 186.

[24] Cheng G., Kurita S., Torigian D.A., Alavi A.: “Current status of sentinel lymph-node biopsy in patients with breast cancer”. Eur. J. Nucl. Med. Mol. Imaging, 2011, 38, 562.