Prognosis of Her2-positive breast cancer has changed since the introduction of trastuzumab for treatment in metastatic and early breast cancer. It was described to be even better compared to prognosis of Her2-negative metastatic breast cancer. The purpose of this study was to evaluate the effect of trastuzumab in our cohort. Besides the effect of adjuvant pretreatment with trastuzumab on survival of patients with metastatic Her2-positive breast cancer was analyzed.
All patients with primary breast cancer of the Regional Breast Cancer Center Dresden diagnosed during the years 2001–2013 were analyzed for treatment with or without trastuzumab in the adjuvant and in the metastatic treatment setting using Kaplan–Meier survival estimation and Cox regression. Age and tumor stage at time of first diagnosis of breast cancer as well as hormone receptor status, grading, time, and site of metastasis at first diagnosis of distant metastatic disease were analyzed.
Of 4.481 female patients with primary breast cancer, 643 presented with metastatic disease. Her2-positive status was documented in 465 patients, including 116 patients with primary or secondary metastases. Median survival of patients with Her2-positive primary metastatic disease was 3.0 years (95% CI 2.3–4.0). After adjustment for other factors, survival was better in patients with Her2-positive breast cancer with trastuzumab therapy compared to Her2-negative metastatic disease (HR 2.10; 95% CI 1.58–2.79). Analysis of influence of adjuvant therapy with and without trastuzumab by Kaplan–Meier showed a trend for better survival in not pretreated patients. Median survival was highest in hormone receptor-positive Her2-positive (triple-positive) primary metastatic breast cancer patients with 3.3 years (95% CI 2.3–4.6).
Prognosis of patients with Her2-positive metastatic breast cancer after trastuzumab treatment is more favorable than for Her2-negative breast cancer. The role of adjuvant chemotherapy with or without trastuzumab warrants further research. Survival is best in triple-positive metastatic breast cancer. This will effect counseling at the time of first diagnosis of metastatic breast cancer.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Kast K, Link T, Friedrich K, Petzold A, Niedostatek A, Schoffer O, Werner C, Klug SJ, Werner A, Gatzweiler A et al (2015) Impact of breast cancer subtypes and patterns of metastasis on outcome. Breast Cancer Res Treat 150(3):621–629
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science (New York, NY) 235(4785):177–182
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874
Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100(14):8418–8423
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792
Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM et al (2014) Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 32(33):3744–3752
Bertaut A, Mounier M, Desmoulins I, Guiu S, Beltjens F, Darut-Jouve A, Ponnelle T, Arnould L, Arveux P (2015) Stage IV breast cancer: a population-based study about prognostic factors according to HER2 and HR status. Eur J Cancer Care 24(6):920–928
Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH (2010) Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 28(1):92–98
Yeo B, Kotsori K, Mohammed K, Walsh G, Smith IE (2015) Long-term outcome of HER2 positive metastatic breast cancer patients treated with first-line trastuzumab. Breast 24(6):751–757
Lambertini M, Ferreira AR, Poggio F, Puglisi F, Bernardo A, Montemurro F, Poletto E, Pozzi E, Rossi V, Risi E et al (2015) Patterns of care and clinical outcomes of first-line trastuzumab-based therapy in HER2-positive metastatic breast cancer patients relapsing after (neo)adjuvant trastuzumab: an Italian Multicenter Retrospective Cohort Study. Oncologist 20(8):880–889
Murthy RK, Varma A, Mishra P, Hess KR, Young E, Murray JL, Koenig KH, Moulder SL, Melhem-Bertrandt A, Giordano SH et al (2014) Effect of adjuvant/neoadjuvant trastuzumab on clinical outcomes in patients with HER2-positive metastatic breast cancer. Cancer 120(13):1932–1938
Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366(2):109–119
Negri E, Zambelli A, Franchi M, Rossi M, Bonifazi M, Corrao G, Moja L, Zocchetti C, La Vecchia C (2014) Effectiveness of trastuzumab in first-line HER2+ metastatic breast cancer after failure in adjuvant setting: a controlled cohort study. Oncologist 19(12):1209–1215
Jackisch C, Welslau M, Schoenegg W, Selbach J, Harich HD, Schroder J, Schmidt M, Gohler T, Eustermann H, Ringel R et al (2014) Impact of trastuzumab treatment beyond disease progression for advanced/metastatic breast cancer on survival—results from a prospective, observational study in Germany. Breast (Edinburgh, Scotland) 23(5):603–608
von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J et al (2011) Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer (Oxford, England: 1990) 47(15):2273–2281
Dawood S, Broglio K, Ensor J, Hortobagyi GN, Giordano SH (2010) Survival differences among women with de novo stage IV and relapsed breast cancer. Ann Oncol 21(11):2169–2174
Metzger-Filho O, de Azambuja E, Procter M, Krieguer M, Smith I, Baselga J, Cameron D, Untch M, Jackisch C, Bell R et al (2016) Trastuzumab re-treatment following adjuvant trastuzumab and the importance of distant disease-free interval: the HERA trial experience. Breast Cancer Res Treat 155(1):127–132
Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Anton A, Lluch A et al (2005) Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 23(19):4265–4274
Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, Flynn PJ, Mailliard JA, Kardinal CG, Krook JE et al (2005) Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer 6(5):425–432
Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M et al (2006) Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 24(18):2786–2792
Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR et al (2011) Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol 29(2):149–156
Rossi V, Nole F, Redana S, Adamoli L, Martinello R, Aurilio G, Verri E, Sapino A, Viale G, Aglietta M et al (2014) Clinical outcome in women with HER2-positive de novo or recurring stage IV breast cancer receiving trastuzumab-based therapy. Breast (Edinburgh, Scotland) 23(1):44–49
Cortesi L, Toss A, Cirilli C, Marcheselli L, Braghiroli B, Sebastiani F, Federico M (2015) Twenty-years experience with de novo metastatic breast cancer. Int J Cancer 137(6):1417–1426
Kitagawa D, Horiguchi S, Yamashita T, Kuroi K, Shimizu K (2014) Comparison of outcomes between women with de novo stage IV and relapsed breast cancer. J Nippon Med Sch 81(3):139–147
Lobbezoo DJ, van Kampen RJ, Voogd AC, Dercksen MW, van den Berkmortel F, Smilde TJ, van de Wouw AJ, Peters FP, van Riel JM, Peters NA et al (2015) Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer? Br J Cancer 112(9):1445–1451
Largillier R, Ferrero JM, Doyen J, Barriere J, Namer M, Mari V, Courdi A, Hannoun-Levi JM, Ettore F, Birtwisle-Peyrottes I et al (2008) Prognostic factors in 1038 women with metastatic breast cancer. Ann Oncol 19(12):2012–2019
Qin T, Yuan ZY, Peng RJ, Bai B, Zeng YD, Shi YX, Teng XY, Liu DG, Wang SS (2015) Clinicopathologic characteristics and prognostic factors for HER2-positive patients with metastatic breast cancer in southern China. Arch Med Sci 11(3):544–550
Tumorzentrum e.V. Dresden.
For this analysis, we exclusively used secondary data. Ethics approval was therefore not necessary.
Informed consent for documentation in the registry and for further research was obtained from all individual patients included in the study.
Conflict of interest
Karin Kast declares to have received honoraries for presentations of Roche, Glaxo Smith Kline, Astra Zeneca, Pfizer, Sanofi Aventis, Novartis, TEVA. Pauline Wimberger declares to be a member of the advisory board of Roche. She also received honoraries for presentations of Roche, Glaxo Smith Kline, Astra Zeneca, Pfizer, Sanofi Aventis, Novartis, TEVA. All other authors declare that they have no competing interests.
No funding was available for this work. The authors declare that they have full control of all primary data and agree to allow the Journal to review their data if requested.
About this article
Cite this article
Kast, K., Schoffer, O., Link, T. et al. Trastuzumab and survival of patients with metastatic breast cancer. Arch Gynecol Obstet 296, 303–312 (2017). https://doi.org/10.1007/s00404-017-4421-x
- Metastatic breast cancer