ideas of this study
Cancer hazard rates reveal more about cancer biology than any other statistical function. Hazard rate in breast cancer proceed through three phases. Following diagnosis and treatment hazard rate rises (AB). By the third year it reaches its maximum whereupon it declines to a minimum (BC). from there and on it gradually rises to a second maximum whereupon the patient dies (CD). This pattern is known as bi-modal hazard (BMH). It is unique to cancer and does not appear in other chronic diseases. It is an epidemiological hallmark of cancer. It is so typical of cancer that it distinguishes cancer from other chronic diseases.
ideas of this study
Data source: Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov)
SEER*Stat Database: Incidence - SEER 9 Regs Public-Use, Nov 2004 Sub (1973-2002),
National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics
Branch, released April 2005, based on the November 2004 submission.
Cancer proceeds through two phases, compensated, when the tumor does not cause any damage or distress, and de-compensated, when the patient suffers. The first peak and trough (ABC) occur during compensation. The ascending part (D) accompanies de compensation which ends in death.
The present studies apply hazard rate fractions: HR = #died / (#live at start of the interval - #lost to follow up)
It is the probability of a patient with breast cancer to die, and is affected also by other ailments the patient may have.
BMH is the common denominator of the following epidemiological phenomena
1. Recurrence following treatment represented here by the publication
of (Karrison et al (1)
Some other publications describing the same pattern:
The relapse rate following breast cancer surgery is bi-modal. (Retsky et al.(2)).
Annual hazard rates of recurrence for breast cancer after primary therapy are bi-modal (Saphner et al (3))
Mammography paradox: The hazard following mammography of young females is higher than in controls Cox (4).
Hazard rates of recurrence following diagnosis of primary breast cancer Jatoi et al. (5)
Hazard rate of recurrence of breast cancer in 3811 spanish patients.
2. Survival following treatment (Ruth Heimann, Samuel Hellman (6)
The steep descent is associated with phase AB of BMH, the tapering off with the BC segment
3. Breast cancer recurrence rate Freedman et al (7)
The ascending curve is associated with the BC segment of BMH
4. Cumulative incidence Nielsen et al (8)
The ascending part is associated with segment AB of BMH. The leveling off, with the BC segment
5. Conditional survival Gloeckler Ries et al (9)
6. Tumor growth rate is proportional to recurrence rate
The improving conditional survival is associated with segment BC of BMH.
All these manifestations may be derived from the BMH using the following relationships:
F(t) - lifetime distribution function
f(t) - the derivative of F(t)
S(t) = 1-F(t) survival function
h(t) = f(t) / S(t) hazard rate
We ought to distinguish between primary hazard or hazard[death] which accounts for death, depicted in the first curve and secondary hazards: hazard[recurrence], and hazard[incidence], which depend on tumor detection and not on death. Survival and conditional survival may be derived directly from hazard[death]. In order to derive secondary hazard from primary we need additional information: tumor growth rate and the resolution power of tumor detecting tools.
Nevertheless all hazard functions point to the same conclusions:
1. AB segment: Hazard rises due to treatment.
2. BC segment: The declining hazard indicates that with time the patient resists cancer better and better. The longer she lives the better her chances to survive. The nature of this resistance is the major concern of this web-site. Although treatment also contributes to this decline, this phenomenon appears in untreated breast cancer and in patients who were treated only once and not treated again later on
The descending portion of BMH appears in all cancers and does not appear in other chronic diseases.
3. CD segment: Marks the final decline when resources are depleted and illness overpowers the patient.
These observations convinced me to propose the following hypothesis.
Cancer is a metabolic deficiency caused by a deficiency of a yet unknown metabolite A. In order to replenish the missing metabolite the organism grows a tumor which produces a substitute B. Since the deficiency continually aggravates, the tumor has to grow more and more in order to replenish the missing metabolite. In advanced deficiency tumor destroys vital functions and finally kills the patient. Tumor ablation aggravates the deficiency and the hazard rises. Patients with micro metastases are protected from therapy induced total ablation and their hazard rate declines.
Clinically this deficiency is manifested by a wasting disease which starts with weight loss and gradually turns into overt cachexia It is named here pernicious cachexia. The tumor protects against cachexia.
Treatment objectives: Do not treat unless the tumor causes pain and distress or destroys vital functions. Wait as long as cancer is compensated and treat only during de compensation.
Farewell my breast
1. Karrison TG,. Ferguson DJ, Meier P. Dormancy of mammary carcinoma after mastectomy
J. National Cancer Institute, (1999) 91 : 80-85.
2. M. Retsky, R. Demicheli and W. J.M. Hrushesky
Does surgery induce angiogenesis in breast cancer? Indirect evidence from relapse pattern and mammography paradox International Journal of Surgery Volume 3, Issue 3 , 2005, Pages 179-187
3. Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after primary therapy J Clin Oncol 1996; 14: 2738-2746.
4. Cox B, Variation in the effectiveness of breast screening by year of follow-up, J Natl Cancer Inst Monogr 22 (1997), pp. 69–72
5. Ismail Jatoi , Anna Tsimelzon , Heidi Weiss , Gary M. Clark and Susan G. Hilsenbeck
Hazard rates of recurrence following diagnosis of primary breast cancer
Breast Cancer Research and Treatment 2005; 89: 2; 173-178
6. Ruth Heimann, Samuel Hellman
Clinical Progression of Breast Cancer Malignant Behavior: What to Expect and When to Expect it.
Journal of Clinical Oncology, Vol 18, Issue 3 (February), 2000: 591
7. GARY M. FREEDMAN, M.D., PENNY R. ANDERSON, M.D., ALEXANDRA L. HANLON, M.S., PH.D.,DEBRA F. EISENBERG, M.S., AND NICOS NICOLAOU, M.D.
PATTERN OF LOCAL RECURRENCE AFTER CONSERVATIVE SURGERYAND WHOLE-BREAST IRRADIATION
Int. J. Radiation Oncology Biol. Phys., Vol. 61, No. 5, pp. 1328–1336,
8. 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
9 Lynn A. Gloeckler Ries, Marsha E. Reichman, Denise Riedel Lewis, Benjamin F. Hankey, Brenda K. Edwards
Cancer Survival and Incidence from the Surveillance, Epidemiology, and End Results (SEER) Program
The Oncologist, Vol. 8, No. 6, 541–552, December 2003