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