Survival in de novo and Recurrent Metastatic Breast Cancer

Institution: Beckman Research Institute of the City of Hope
Investigator(s): Sumanta Pal, M.D. -
Award Cycle: 2009 (Cycle 15) Grant #: 15IB-0140 Award: $249,000
Award Type: IDEA
Research Priorities
Detection, Prognosis and Treatment>Innovative Treatment Modalities: search for a cure

Initial Award Abstract (2009)

It is unclear whether newer chemotherapy agents have, in fact, improved overall patient survival overall. We have previously reported data from the City of Hope Comprehensive Cancer Center (COHCCC) registry which suggests that there is no improvement in survival for patients with metastatic breast cancer treated in two consecutive decades (between 1985 and 1994, or between 1995 and 2004). This finding was irrespective of the use of chemotherapy. Importantly, the patients considered in this analysis all had metastatic disease at the time of their original diagnosis of breast cancer.

In this project we will expand our analysis to also include patients who have had localized breast cancer that has spread to distant sites (referred to as recurrent metastatic breast cancer). The key clinical questions we will address include:
~ For patients who have had a recurrence metastatic breast cancer, have advances in chemotherapy affected survival?
~ Is there a difference in survival amongst patients who have recurrent metastatic breast cancer, as compared to those patients who present initially with metastatic disease (i.e., the group of patients included in our original analysis)?

For these studies we will obtain information regarding survival of patients with recurrent metastatic breast cancer treated with chemotherapy. We will divide these patients into two groups (patients diagnosed between 1985 and 1994, or between 1995 and 2004), and compare survival amongst these two groups. We will try to account for factors that may influence survival in these groups (for instance, the amount of time between the initial diagnosis of breast cancer and the diagnosis of metastatic disease). Finally, we will compare survival in the group analyzed in the previous study (patients who initially present with metastatic disease) and compare to survival in patients with recurrent metastatic breast cancer.

Thus, this study may be the first to indicate differences in survival trends with chemotherapy in these two disease processes, and may ultimately lead to a change in the current therapeutic approach for both. Furthermore, these data may serve as the rationale for laboratory explorations of biological differences between de novo and recurrent MBC, perhaps yielding novel drug targets for both.

Final Report (2011)

Survival in metastatic breast cancer has improved over the past several decades, but it is unclear whether cytotoxic agents have contributed substantially to this improvement. We assessed the survival of patients with de novo and recurrent metastatic breast cancer treated at our institution, and specifically ascertained whether they had received chemotherapeutic agents developed and approved for metastatic breast cancer after 1995 or before 1995. This was a landmark year, with the approval of paclitaxel chemotherapy. Multiple other chemotherapeutic agents have ensued.

The project carried two specific aims:

  1. Is there an improvement in survival (from the time of diagnosis with distant metastasis)amongst patients treated for MBC (both recurrent and de novo) in the pre- and post-paclitaxel era?
  2. Is there a difference in survival (from the time of diagnosis with distant metastasis) in patients with recurrent MBC as compared to patients with de novo MBC?

A major barrier to the proposed research was the ability to collect a comprehensive "chemotherapy history" for each patient with metastatic breast cancer. At a tertiary care hospital such as City of Hope, where multiple lines of therapy may have been rendered elsewhere, obtaining a comprehensive history can be challenging. Nonetheless, we encountered many patients in our registry that had been treated with systemic therapies for breast cancer over the course of several years.

A major accomplishment of the project was to delineate the fact that novel chemotherapeutic agents have not resulted in a marked improvement in survival amongst patients with de novo metastatic breast cancer. This has recently been summarized in a manuscript which is pending review in BMC Cancer. Now that a database has been established including the majority of patients treated at City of Hope, in the future, we will be able to mine for other clinic-pathologic characteristics predictive of survival.

Male breast cancer: an update in diagnosis, treatment and molecular profiling.
Index Medicus: Maturitas
Authors: Onami S, Ozaki M, Mortimer JE, Pal SK
Yr: 2010 Vol: 65 Nbr: 4 Abs: Pg:308-14

Evaluating the older patient with cancer: understanding frailty and the geriatric assessment.
Periodical:CA: A Cancer Journal for Clinicians
Index Medicus: CA Cancer J Clin
Authors: Pal SK, Katheria V, Hurria A
Yr: 2010 Vol: 60 Nbr: 2 Abs: Pg:120-32

Papillary carcinoma of the breast: an overview.
Periodical:Breast Cancer Research and Treatment
Index Medicus: Breast Cancer Res Treat
Authors: Pal SK, Lau SK, Kruper L, et al.
Yr: 2010 Vol: 122 Nbr: 3 Abs: Pg:637-45

Akt inhibitors in clinical development for the treatment of cancer.
Periodical:Expert Opinion on Investigational Drugs
Index Medicus: Expert Opin Investig Drugs
Authors: Pal SK, Reckamp K, Yu H, Figlin RA
Yr: 2010 Vol: Sept Nbr: Abs: Pg:ePub

Deciphering the anticancer mechanisms of sunitinib.
Periodical:Cancer Biology and Therapy
Index Medicus:
Authors: Pal SK, Figlin RA, Yu H
Yr: 2010 Vol: 10 Nbr: 7 Abs: Pg:ePub

Treatment Options in Metastatic Renal Cell Carcinoma: Focus on mTOR Inhibitors.
Periodical:Clinical Medicine Insights: Oncology
Index Medicus: Clin Med Insights Oncol
Authors: Pal SK, Figlin RA
Yr: 2010 Vol: 4 Nbr: Abs: Pg:43-53

Cognitive changes associated with endocrine therapy for breast cancer.
Index Medicus: Maturitas
Authors: Agrawal K, Onami S, Mortimer JE, Pal SK
Yr: 2010 Vol: Aug Nbr: Abs: Pg:ePub

Targeted therapies: Pazopanib: carving a niche in a crowded therapeutic landscape.
Periodical:Nature Revieww, Clinical Oncology
Index Medicus: Nat Rev Clin Oncol
Authors: Pal SK, Figlin RA
Yr: 2010 Vol: 7 Nbr: 7 Abs: Pg:362-3

Targeted therapies for non-small cell lung cancer: an evolving landscape.
Periodical:Molecular Cancer Therapeutics
Index Medicus: Mol Cancer Ther
Authors: Pal SK, Figlin RA, Reckamp K
Yr: 2010 Vol: 9 Nbr: 7 Abs: Pg:1931-44