Advances in treatment and care in metastatic breast cancer (MBC): are there MBC patients who are curable?
Review Article

Advances in treatment and care in metastatic breast cancer (MBC): are there MBC patients who are curable?

Masaya Hattori, Hiroji Iwata

Department Breast Oncology, Aichi Cancer Center, kusa-ku, Nagoya, Japan

Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: None; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Masaya Hattori. Department of Breast Oncology, Aichi Cancer Center, 1-1 Kanokoden, kusa-ku, Nagoya, 464-8681, Japan. Email:; Hiroji Iwata. Department of Breast Oncology, Aichi Cancer Center, 1-1 Kanokoden, kusa-ku, Nagoya, 464-8681, Japan. Email:

Abstract: Metastatic breast cancer (MBC) remains a largely incurable disease. The goals of treatment for MBC are still to maintain quality of life and prolong survival. However, some cases of MBC with a long-term relapse free survival occurs, implying that a small subset of MBC patients could become curable. Although it is a controversial issue of whether MBC can be cured, a more aggressive multidisciplinary approach to MBC with a curable intent may help improve MBC patient outcomes. The Earlier detection of metastatic disease by using modern imaging technologies may allow the detection of metastasis before cancer cells spread widely. This brief review focuses on the potentials of clinical response at initial therapy of MBC and early detection of metastatic disease of the possibility of cure of MBC patients.

Keywords: Oligometastasis (OM); early detection; metastatic breast cancer (MBC); clinical complete response

Submitted Mar 28, 2018. Accepted for publication May 03, 2018.

doi: 10.21037/cco.2018.05.01


Breast cancer is the second most common cancer in the world and the most frequent cancer among women. with approximately 1.7 million new cancer cases diagnosed yearly (1). Despite improvements in the early detection of breast cancer and the development of more effective systemic therapies, about 30% of patients with early disease will relapse with distant metastases (2), and metastatic disease remains the leading cause of death in those patients with breast cancer (3). Rapid evolution of targeted therapies and understandings of molecular biology and genetics of breast cancer have improved metastatic breast cancer (MBC) outcomes in recent years (4,5), however, many physicians still believe that the metastatic disease remains largely incurable, and the goals of treatment for MBC are to delay disease progression and to prolong survival with maintaining a good quality of life. However, many physicians also experience that it is possible to obtain long-term survival using standard treatments in a small number of cases (6).

Molecular subtypes and clinical complete response (CR)

Trastuzumab has significantly improved survival of patients with HER2-positive MBC (7). We especially experience the case with a high probability of being curable disease in patients with HER2-positive MBC. There have been several reports of durable clinical CR with HER2-positive MBC treated with anti-HER2 therapy (8-10). Niikura et al. (11) assessed 108 HER2-positive MBC patients who received trastuzumab for more than 2 years as the first-line treatment. They showed that more than 80% of patients survive 10 years after the diagnosis of MBC, and more than half of patients achieved clinical CR. And they also showed that 21 patients with CR had not experienced disease progression even after the interruption of trastuzumab therapy. Gullo et al. (12) showed 6 of 13 cases with achieving CR after receiving trastuzumab together with their first-line chemotherapy remain alive and continuously cancer free. Witzel et al. (13) identified 268 patients with HER2-positive MBC who had not progressed for at least 2 years on trastuzumab. They showed that 47.1% of patients remained in remission for more than 5 years, and achieving CR after initial trastuzumab treatment was one of the factors associated with longer time to progression. Yeo et al. (14) reported 25 HER2-positive MBC patients who remained in remission more than 5 years, and showed a trend towards improved PFS in those patients who achieved CR. These data may indicate that a small proportion of patients with HER2-positive MBC have a potential of cure, and also suggest that achieving clinical CR with first-line therapy is important for durable CR. Moreover, Rahman et al. (15) showed that the outcome of MBC patients obtaining clinical CR with first-line doxorubicin-containing chemotherapy was better than for patients without clinical CR. Therefore, achieving clinical CR with initial treatment may be one of the goals of MBC patients. It is notable that the rate of clinical CR is much higher in patients with HER2-positive MBC than other molecular subtypes. However, even MBC with other molecular subtypes (6), there may be a potential of cure if clinical CR can be achieved at initial treatment with effective combination of chemotherapy and targeted therapy.

Oligometastasis (OM)

The MBC patients with OM, which is characterized by solitary or few detectable metastatic lesions, has been identified approximately 1–10% of newly diagnosed patients with stage IV disease, and are potentially curable (16,17). It is currently unclear whether radical local therapy for OM is beneficial or not, however, a more aggressive and multidisciplinary approach before the cancer cells spread widely could lead to be curable. Kobayashi et al. (18) identified 75 cases with OM breast cancer in their 30-year experience, and showed a 10-year overall survival rate (OSR) of 59.2% and a 10-year relapse-free rate (RFR) of 27.4%. They also showed that the cases with only single organ involvement were associated with a better survival (a 10-year OSR of 73% and a 10-year RFR of 42%) and the cases achieved CR by multidisciplinary treatments survived longer than the cases with partial response or stable disease. Hanrahan et al. (16) summarized the outcomes of Stage IV breast carcinoma with no evidence of clinically measurable disease by surgical resection and/or irradiation with curative intent in four phase II trials. They showed a 5-year disease-free survival (DFS) of 34% and 5-year OS of 59% in the docetaxel-based trial, and showed both 20-year DFS and OS of 26% in the 3 doxorubicin-based studies. The European School of Oncology-Metastatic Breast Cancer (ESO-MBC) Task Force stated in their consensus recommendations; “A small but very important subset of MBC patients, for example, those with a solitary metastatic lesion, can achieve complete remission and a long survival. A more aggressive and multidisciplinary approach should be considered for these selected patients. A clinical trial addressing this specific situation is needed.” (17). However, early detection of patients with OM which considered as an intermediate biological state between localized and widely metastatic disease is challenging. Surveillance guidelines (19,20) for breast cancer patients after surgery recommend regular follow-up with mammography, history, and physical examination, but additional routine laboratory or radiographic investigations for asymptomatic patients are not recommended because there is no evidence of improved clinical outcomes associated with the early detection of distant metastasis. However, the recommendations of these guidelines were based on data from clinical trials reported in the 1990s (21,22). Recent advances in imaging technologies including, for instance, helical CT, bone scintigraphy, PET and MRI allows the very early detection of distant metastases. Therefore, more intensive postsurgical surveillance with using modern imaging technologies may improve early detection of distant metastases, especially in patients with high-risk breast cancer. In Japan, we currently started a prospective randomized Phase III trial (23) for confirming to the superiority of intensive follow-up in terms of OS over standard follow-up in high-risk breast cancer patients. The intensive follow-up group undergo physical examination, bone scintigraphy, chest computed tomography, abdominal computed tomography, brain magnetic resonance imaging/computed tomography and frequent tumor marker evaluations, whereas the standard follow-up group undergo physical examination at the same frequency and tumor markers will be evaluated once a year.


The rapid advances in molecular biology and evolving treatment options have led to the improvement of survival in patients with MBC. As we indicated, there is reasonable evidence to suggest that some MBC patients could be cured, although it is currently still a small number. MBC is considered generally incurable, but we believe there are the patients who can aim to cure. Advances in treatment based on understanding of molecular biology could offer the attainment of clinical CR with first-line treatment of MBC patients and may provide the patients with possibility of cure. Advances in imaging technologies could offer the study aimed at a cure of early MBC. In the future, new strategies for MBC could standardize with a curable intent.




Conflicts of Interest: The authors have no conflicts of interest to declare.


  1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86. [Crossref] [PubMed]
  2. Early Breast Cancer Trialists' Collaborative G. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-717. [Crossref] [PubMed]
  3. Redig AJ, McAllister SS. Breast cancer as a systemic disease: a view of metastasis. J Intern Med 2013;274:113-26. [Crossref] [PubMed]
  4. Giordano SH, Buzdar AU, Smith TL, et al. Is breast cancer survival improving? Cancer 2004;100:44-52. [Crossref] [PubMed]
  5. Sundquist M, Brudin L, Tejler G. Improved survival in metastatic breast cancer 1985-2016. Breast 2017;31:46-50. [Crossref] [PubMed]
  6. Iwata H. Future treatment strategies for metastatic breast cancer: curable or incurable? Breast Cancer 2012;19:200-5. [Crossref] [PubMed]
  7. Dawood S, Broglio K, Buzdar AU, et al. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 2010;28:92-8. [Crossref] [PubMed]
  8. Cantini L, Pistelli M, Savini A, et al. Long-responders to anti-HER2 therapies: A case report and review of the literature. Mol Clin Oncol 2018;8:147-52. [PubMed]
  9. Ihnenfeld Arcienega I, Imesch P, Fink D, et al. Prolonged complete remission of metastatic HER2-positive breast cancer after continuous trastuzumab treatment: a case report and review of the literature. Target Oncol 2015;10:297-301. [Crossref] [PubMed]
  10. Hsieh A, Pittman K, Patterson WK, et al. Can maintenance trastuzumab be stopped in patients with HER2-positive metastatic breast cancer? BMJ Case Rep 2015;2015. [Crossref] [PubMed]
  11. Niikura N, Shimomura A, Fukatsu Y, et al. Durable complete response in HER2-positive breast cancer: a multicenter retrospective analysis. Breast Cancer Res Treat 2018;167:81-7. [Crossref] [PubMed]
  12. Gullo G, Zuradelli M, Sclafani F, et al. Durable complete response following chemotherapy and trastuzumab for metastatic HER2-positive breast cancer. Ann Oncol 2012;23:2204-5. [Crossref] [PubMed]
  13. Witzel I, Muller V, Abenhardt W, et al. Long-term tumor remission under trastuzumab treatment for HER2 positive metastatic breast cancer - results from the HER-OS patient registry. BMC Cancer 2014;14:806. [Crossref] [PubMed]
  14. Yeo B, Kotsori K, Mohammed K, et al. Long-term outcome of HER2 positive metastatic breast cancer patients treated with first-line trastuzumab. Breast 2015;24:751-7. [Crossref] [PubMed]
  15. Rahman ZU, Frye DK, Smith TL, et al. Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: a reference. Cancer 1999;85:104-11. [Crossref] [PubMed]
  16. Hanrahan EO, Broglio KR, Buzdar AU, et al. Combined-modality treatment for isolated recurrences of breast carcinoma: update on 30 years of experience at the University of Texas M.D. Anderson Cancer Center and assessment of prognostic factors. Cancer 2005;104:1158-71. [Crossref] [PubMed]
  17. Pagani O, Senkus E, Wood W, et al. International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst 2010;102:456-63. [Crossref] [PubMed]
  18. Kobayashi T, Ichiba T, Sakuyama T, et al. Possible clinical cure of metastatic breast cancer: lessons from our 30-year experience with oligometastatic breast cancer patients and literature review. Breast Cancer 2012;19:218-37. [Crossref] [PubMed]
  19. Aebi S, Davidson T, Gruber G, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2011;22 Suppl 6:vi12-24. [Crossref] [PubMed]
  20. Khatcheressian JL, Hurley P, Bantug E, et al. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31:961-5. [Crossref] [PubMed]
  21. Rosselli Del Turco M, Palli D, Cariddi A, et al. Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. National Research Council Project on Breast Cancer follow-up. JAMA 1994;271:1593-7. [Crossref] [PubMed]
  22. Palli D, Russo A, Saieva C, et al. Intensive vs clinical follow-up after treatment of primary breast cancer: 10-year update of a randomized trial. National Research Council Project on Breast Cancer Follow-up. JAMA 1999;281:1586. [Crossref] [PubMed]
  23. Hojo T, Masuda N, Mizutani T, et al. Intensive vs. Standard Post-Operative Surveillance in High-Risk Breast Cancer Patients (INSPIRE): Japan Clinical Oncology Group Study JCOG1204. Jpn J Clin Oncol 2015;45:983-6. [Crossref] [PubMed]
Cite this article as: Hattori M, Iwata H. Advances in treatment and care in metastatic breast cancer (MBC): are there MBC patients who are curable? Chin Clin Oncol 2018;7(3):23. doi: 10.21037/cco.2018.05.01