The relationship between breast cancer recurrence and bi-modal hazard rate (BMH)

The following graph illustrates the pattern of breast cancer recurrence following diagnosis and treatment. Initially it rises steeply and gradually tapers off. The hazard rate of recurrence ascends to a maximum whereupon it declines.

The two graphs illustrate the relationship between cumulative recurrence and its hazard., which received the name bi-modal hazard.(BMH) . The steep ascending part of the cumulative curve is coincides with the high hazard. The the gradual flattening of the cumulative curve accounts for the declining hazard. Both curves are epidemiological hallmarks of breast cancer, which are interpreted as follows:

1.The first BMH peak indicates that in the early stage of cancer, patient depends upon her tumor and its removal accounts for the rising hazard. After the third year hazard declines for several years. However as cancer progresses tumor impinges upon vital functions and the hazard rises again.

2. The leveling off of the cumulative curve reflects the declining hazard. During this period, the prospect of the cancer patient continually improves. The longer she lives the better her chances to survive. During this period the patient mobilizes healing processes which are still unknown to us, and appears healthy.

Similar failure rate curves were published in the literature. Here are three examples:

Failure pattern among high risk breast cancer patients

Nielsen et al (1) studied the failure pattern among high risk breast cancer patients. Their was to examine the overall disease recurrence pattern among patients randomly assigned to receive treatment with or without radiotherapy (RT). The 18-year probability of any first breast cancer event was 73% and 59% (P < .001) after no RT and RT, respectively .

The end points considered were loco -regional recurrence (LRR), distant metastases (DM), and contra-lateral breast cancer (CBC). LRR was defined as an ipsilateral chest wall failure (local) or ipsilateral axillary or supra/infraclavicular failure (regional). LRR alone was defined as an LRR with no sign of subsequent DM within 1 month, whereas patients with LRR followed by DM within the same month were recorded as simultaneous failures (simLRR-DM).

The following figure was copied from their publication

The curve ascends rapidly and gradually tapers off. The hazard rate of distant metastases declines.

Breast cancer recurrence pattern

A similar recurrence pattern was described by Early Breast Cancer Trialists' Collaborative Group (EBCTCG). In their introduction they write:

In early breast cancer, disease is detected only in the breast or, in the case of women with node-positive disease, the breast and locoregional lymph nodes, and all detected disease can be removed surgically. However, undetected deposits of disease may remain either locally or at distant sites that, if untreated, could over the next 5, 10, 15, or more years develop into a life-threatening clinical recurrence. Breast cancer is unusual in that although the risk of distant recurrence is greatest during the first decade, it may still be substantial during the second decade after diagnosis. recurrence rate, and improve long-term survival”.

Figure 2. Polychemotherapy versus not, by entry age <50 or 50–69 years: 15-year probabilities of recurrence and of breast cancer mortality

Loco-regional recurrence

Wallgren et al studied “Risk Factors for Locoregional Recurrence Among Breast Cancer Patients ”(3)

Fig 3. Cumulative incidence functions for locoregional failure ± distant failure according to risk group for pre menopausal patients with node-positive disease. pts, patients.


1. Hanne M. Nielsen, Marie Overgaard, Cai Grau, Anni R. Jensen, Jens Overgaard
Study of Failure Pattern Among High-Risk Breast Cancer Patients With or Without Postmastectomy
Radiotherapy in Addition to Adjuvant Systemic Therapy: Long-Term Results From the Danish Breast Cancer Cooperative Group DBCG 82 b and c Randomized Studies

Journal of Clinical Oncology, Vol 24, No 15 (May 20), 2006: pp. 2268-2275

2. Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials .

The Lancet, Volume 365, Issue 9472, 14 May 2005-20 May 2005, Pages 1665-1666
S Chia, C Bryce, K Gelmon

3. A. Wallgren, M. Bonetti, R.D. Gelber, A. Goldhirsch, M. Castiglione-Gertsch, S.B. Holmberg, J. Lindtner, B. Thürlimann, M. Fey, I.D. Werner, J.F. Forbes, K. Price, A.S. Coates, J. Collins
Risk Factors for Locoregional Recurrence Among Breast Cancer Patients: Results From International Breast Cancer Study Group Trials I Through VII
Journal of Clinical Oncology, Vol 21, Issue 7 (April), 2003: 1205-1213

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