Prognostic and predictive factors in metastatic breast cancer
- Stephen Chia, MD, FRCPC
Stephen Chia, MD, FRCPC
- Associate Professor of Medicine
- British Columbia Cancer Agency
Although metastatic breast cancer (MBC) is unlikely to be cured, meaningful improvements in survival have been seen, coincident with the introduction of newer systemic therapies [1-3]. Median overall survival (OS) approaches two years, although this can range from a few months to many years . As greater knowledge is generated regarding the specific molecular alterations associated with individual breast cancers, it will be of paramount importance to distinguish the differences between the multitude of prognostic factors likely expressed versus the few predictive factors that will help select specific therapy(s).
This topic reviews prognostic factors for patients with metastatic breast cancer. A further discussion of prognostic and predictive factors utilized in primary breast cancer (for patients with non-metastatic disease) is covered separately. (See "Prognostic and predictive factors in early, nonmetastatic breast cancer".)
PROGNOSTIC VERSUS PREDICTIVE FACTORS
By definition, a prognostic factor is capable of providing information on clinical outcome at the time of diagnosis, or at various times during the patient’s course with metastatic disease, independent of therapy. Such markers are usually indicators of growth, invasion, and metastatic potential [5,6]. In contrast, a predictive factor is capable of providing information on the likelihood of response to a given therapeutic modality. Such markers are either within the target of the treatment, the surrounding stroma, or serve as modulators or epiphenomena related to expression and/or function of the target. Although they can be separately classified, several factors in breast cancer are both prognostic and predictive (eg, the presence of over-expression of the human epidermal growth factor receptor 2 [HER2]).
The most useful prognostic factors are clinically based. While circulating tumor cells (CTCs) are also prognostic, their role in the clinical management of patients with metastatic breast cancer is not clear.
Clinical factors — The effect of clinical factors on prognosis is summarized below:
- Chia SK, Speers CH, D'yachkova Y, et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer 2007; 110:973.
- Gennari A, Conte P, Rosso R, et al. Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer 2005; 104:1742.
- Dafni U, Grimani I, Xyrafas A, et al. Fifteen-year trends in metastatic breast cancer survival in Greece. Breast Cancer Res Treat 2010; 119:621.
- Greenberg PA, Hortobagyi GN, Smith TL, et al. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996; 14:2197.
- Gasparini G, Pozza F, Harris AL. Evaluating the potential usefulness of new prognostic and predictive indicators in node-negative breast cancer patients. J Natl Cancer Inst 1993; 85:1206.
- Hayes DF, Trock B, Harris AL. Assessing the clinical impact of prognostic factors: when is "statistically significant" clinically useful? Breast Cancer Res Treat 1998; 52:305.
- Swenerton KD, Legha SS, Smith T, et al. Prognostic factors in metastatic breast cancer treated with combination chemotherapy. Cancer Res 1979; 39:1552.
- Hortobagyi GN, Smith TL, Legha SS, et al. Multivariate analysis of prognostic factors in metastatic breast cancer. J Clin Oncol 1983; 1:776.
- Clark GM, Sledge GW Jr, Osborne CK, McGuire WL. Survival from first recurrence: relative importance of prognostic factors in 1,015 breast cancer patients. J Clin Oncol 1987; 5:55.
- Harris JR, Hellman S. Observations on survival curve analysis with particular reference to breast cancer treatment. Cancer 1986; 57:925.
- Robertson JF, Dixon AR, Nicholson RI, et al. Confirmation of a prognostic index for patients with metastatic breast cancer treated by endocrine therapy. Breast Cancer Res Treat 1992; 22:221.
- Barrios CH, Sampaio C, Vinholes J, Caponero R. What is the role of chemotherapy in estrogen receptor-positive, advanced breast cancer? Ann Oncol 2009; 20:1157.
- Stuart-Harris R, Shadbolt B, Palmqvist C, Chaudri Ross HA. The prognostic significance of single hormone receptor positive metastatic breast cancer: an analysis of three randomised phase III trials of aromatase inhibitors. Breast 2009; 18:351.
- Emi Y, Kitamura K, Shikada Y, et al. Metastatic breast cancer with HER2/neu-positive cells tends to have a morbid prognosis. Surgery 2002; 131:S217.
- Ismail-Khan R, Bui MM. A review of triple-negative breast cancer. Cancer Control 2010; 17:173.
- Yamamoto N, Watanabe T, Katsumata N, et al. Construction and validation of a practical prognostic index for patients with metastatic breast cancer. J Clin Oncol 1998; 16:2401.
- Leivonen MK, Kalima TV. Prognostic factors associated with survival after breast cancer recurrence. Acta Oncol 1991; 30:583.
- Cristofanilli M, Hayes DF, Budd GT, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 2005; 23:1420.
- Hayes DF, Cristofanilli M, Budd GT, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 2006; 12:4218.
- Cristofanilli M, Broglio KR, Guarneri V, et al. Circulating tumor cells in metastatic breast cancer: biologic staging beyond tumor burden. Clin Breast Cancer 2007; 7:471.
- Dawood S, Broglio K, Valero V, et al. Circulating tumor cells in metastatic breast cancer: from prognostic stratification to modification of the staging system? Cancer 2008; 113:2422.
- Budd GT, Cristofanilli M, Ellis MJ, et al. Circulating tumor cells versus imaging--predicting overall survival in metastatic breast cancer. Clin Cancer Res 2006; 12:6403.
- Zhang L, Riethdorf S, Wu G, et al. Meta-analysis of the prognostic value of circulating tumor cells in breast cancer. Clin Cancer Res 2012; 18:5701.
- Smerage JB, Barlow WE, Hortobagyi GN, et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol 2014; 32:3483.
- Bidard FC, Peeters DJ, Fehm T, et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 2014; 15:406.
- Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 2007; 25:5287.
- Prat A, Cheang MC, Galván P, et al. Prognostic Value of Intrinsic Subtypes in Hormone Receptor-Positive Metastatic Breast Cancer Treated With Letrozole With or Without Lapatinib. JAMA Oncol 2016; 2:1287.
- King TA, Lyman JP, Gonen M, et al. Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013. J Clin Oncol 2016; 34:2359.
- de Dueñas EM, Hernández AL, Zotano AG, et al. Prospective evaluation of the conversion rate in the receptor status between primary breast cancer and metastasis: results from the GEICAM 2009-03 ConvertHER study. Breast Cancer Res Treat 2014; 143:507.
- Amir E, Clemons M, Purdie CA, et al. Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies. Cancer Treat Rev 2012; 38:708.
- Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007; 25:118.
- Wolff AC, Hammond ME, Hicks DG, et al. Reply to R. Bhargava et al and K. Lambein et al. J Clin Oncol 2014; 32:1857.
- Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 2010; 28:2784.
- Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490:61.
- Curtis C, Shah SP, Chin SF, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012; 486:346.
- André F, Bachelot T, Commo F, et al. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol 2014; 15:267.
- PROGNOSTIC VERSUS PREDICTIVE FACTORS
- PROGNOSTIC FACTORS
- Clinical factors
- Circulating tumor cells
- Gene expression analyses
- PREDICTIVE FACTORS
- Tests done on breast tissue
- - Hormone receptors
- - HER2 overexpression
- - Other tests
- Serum tumor markers
- Next generation sequencing of breast tumors
- SUMMARY AND RECOMMENDATIONS