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Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma

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Abstract

Purpose

Metastatic pancreatic adenocarcinoma is considered a uniformly fatal disease with a median survival of 1 year with modern chemotherapy. While a subset of patients achieve prolonged survival, few of the factors that define this group of patients are known.

Methods

For the determination of overall survival (OS), 549 patients with histologically confirmed metastatic pancreatic adenocarcinoma were evaluated. Emphasis was placed on treatment history and family history of breast, ovarian, and pancreatic cancers. To ensure a uniform metastatic population, patients treated with prior locoregional therapies (i.e., surgery or radiotherapy) were excluded as were patients with a prior history of stage I–III disease.

Results

Patients with family history or pedigree history of cancer had superior OS. This was especially true in patients with three or more relatives with either breast, ovarian, or pancreatic cancers [hazard ratio (HR) 0.49, 95 % confidence interval (CI) 0.30–0.80, p = 0.003]. First-line platinum chemotherapy was associated with a poor survival (hazard ratio for death 1.74, 95 % CI 1.12–2.71, p = 0.01) for patients without a family history of these cancers but not for those without such a history (p = 0.31). In fact, as the number of relatives with these cancers increased, the OS survival improved for individuals receiving first-line platinum therapy (HR 0.76, 95 % CI 0.65–0.89, p = 0.0004), which was not the case for those receiving other therapies (p = 0.98).

Conclusions

Treatment with platinum chemotherapy in patients with a family history of breast, ovarian, or pancreatic cancers was associated with a longer survival, whereas platinum use in patients without such a family history of cancer was associated with poor survival. These findings suggest that family history may serve as a predictive marker for platinum use in patients with metastatic pancreatic adenocarcinoma.

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Acknowledgments

This work is supported by The Swim Across America Laboratory at Johns Hopkins, The Banyan Gate Foundation, The Lustgarten Foundation for Pancreatic Cancer Research and Gastrointestinal SPORE grant P50CA062924 

Conflict of interest

Dr. Diaz is a founder and shareholder of Papgene Inc. and Personal Genome Diagnostics and licensed technology to these and other entities. These relationships are managed by the Johns Hopkins conflict of interest committee.  These items disclosed by Dr. Diaz are not related to contents of this article. Dr. Klein notes that under a licensing agreement between Myriad Genetics Inc. and the Johns Hopkins University, Drs. Klein is entitled to a share of royalty received by the University on sales of products. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies. Other co-authors declare no conflict of interest with the contents of this article.

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Author notes

    Authors and Affiliations

    1. Swim Across America Laboratory, Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins, 1650 Orleans Street, CRB I Room 590, Baltimore, MD, 21231, USA

      Luis A. Diaz Jr.

    2. Sidney Kimmel Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD, 21231, USA

      Elizabeth A. Sugar, George Oliver, Daniel Laheru & Luis A. Diaz Jr.

    3. Departments of Pathology and Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, 21205, USA

      Alison Klein & Christine Alewine

    4. Departments of Biostatistics and Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA

      Elizabeth A. Sugar

    5. Department of G.I. Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX, 77030, USA

      David Fogelman, Neeraj Shah, Milind Javle, Rachna Shroff, Robert A. Wolff & James L. Abbruzzese

    6. University of Texas/M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX, 77096, USA

      David Fogelman, Milind Javle & Robert A. Wolff

    7. Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E3537, Baltimore, MD, 21205, USA

      Elizabeth A. Sugar

    8. 6300 Harry Hines Blvd. Ste 265, Dallas, TX, 75235, USA

      George Oliver

    9. Staten Island University Hospital, 475 Seaview Avenue, Staten Island, NY, 10305, USA

      Neeraj Shah

    10. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, 1650 Orleans St., Rm G89, Baltimore, MD, 21231-1000, USA

      Alison Klein & Daniel Laheru

    11. Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, USA

      Alison Klein

    12. Johns Hopkins Bloomberg School of Public Health, 1650 Orleans Street, CRB I Room 590, Baltimore, MD, 21231, USA

      Alison Klein

    13. Department of Medical Oncology, NCI-National Cancer Institute, 10 Center Dr, Bldg 10/12N226, Bethesda, MD, 20892, USA

      Christine Alewine

    14. 1515 Holcombe Blvd., Unit 0085, Houston, TX, 77030, USA

      Huamin Wang

    15. Division of Medical Oncology, Duke University, 10 Searle Drive, 445 Seeley G Mudd Building, Durham, NC, 27710, USA

      James L. Abbruzzese

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    1. David Fogelman
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    Correspondence to Luis A. Diaz Jr..

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    David Fogelman, Elizabeth A. Sugar, and George Oliver have contributed equally to this manuscript.

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    Fogelman, D., Sugar, E.A., Oliver, G. et al. Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma. Cancer Chemother Pharmacol 76, 489–498 (2015). https://doi.org/10.1007/s00280-015-2788-6

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    • DOI: https://doi.org/10.1007/s00280-015-2788-6

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