Kathleen I. Pritchard

Last updated
Kathleen I. Pritchard
NationalityCanadian
Alma materQueen's University
Occupation(s)Medical oncologist
Clinical trials research scientist
AwardsO. Harold Warwick Prize

Kathleen I. Pritchard, CM is the head of oncology at Sunnybrook Health Sciences Centre in Toronto, Canada, [1] specializing in breast cancer therapies, and leading the clinical trials division of the centre. [2] She has authored numerous studies on women's health, breast cancer, hormone replacement therapy, public health, and research methodology. [3] According to Thomson Reuters, Pritchard was one of the most cited researchers in the world in 2014 [3] [4] and 2015. [5]

Contents

Biography

Kathleen I. Pritchard, CM, grew up in Deep River, Ontario. [6] She graduated from the local high school in 1964. [6] She earned her Bachelor's in Science in 1968 from Queen's University in Kingston, Ontario and attained her medical degree there in 1971. Her practicum in Internal Medicine was completed at Wellesley Hospital, Toronto Western Hospital, and Toronto General Hospital. Between 1973 and 1974 at the University of Toronto, Pritchard focused on research into melanoma and tumor immunology, and then in 1977 began researching breast cancer in clinical trials as a research fellow at the University of Toronto. [7]

Between 1978 and 1984, Pritchard conducted clinical trials at Women's College Hospital under an award granted by the National Cancer Institute of Canada (NCIC). In 1984, she was appointed head of Medical Oncology and Haematology at Women's College Hospital and chair of the Breast Cancer Site Group of the NCIC. Three years later, Pritchard moved to the Sunnybrook Regional Cancer Centre in Toronto [7] where she has served as head of Medical Oncology. [1] A decade later, in 1997, she was appointed to head the Clinical Trials and Epidemiology at the Odette Cancer Centre of Sunnybrook. She has been involved in numerous studies and is one of Canada's most-known academic physicians, [7] researching such topics as chemotherapy verses hormone therapy, [8] the effects of aging and menopause for risk of breast cancer, [9] and drugs which aid in non-recurrence. [10]

Research

Pritchard is an oncologist and researcher with involvement in numerous clinical studies. Her research spans a range of topics, but it focuses primarily on women's health and breast cancer therapies. Her research goals include the development of individualized patient therapies and the advancement of prognostic tests. Some of her research investigates the use of genetic factors to predict disease progression and to formulate tailored treatment plans. In addition to looking at genetics, Pritchard's research aims to better understand primary and secondary combination treatments, taking into account the patient's age and stage in life. Pritchard's clinical trials have yielded findings that have transformed breast cancer treatment approaches worldwide. Pritchard is published in numerous significant journals of oncology, including The New England Journal of Medicine , Journal of the National Cancer Institute , Journal of Clinical Oncology , The Lancet , and The Lancet Oncology . [11]

One of Pritchard's self-proclaimed "eureka" moments was in a clinical trial concerning the use of the drug letrozole as an adjuvant therapy in postmenopausal women who had taken tamoxifen for five years as a primary breast cancer treatment. Letrozole is an aromatase inhibitor that reduces estrogen production, which is necessary for tumor growth. Pritchard followed over 5,000 postmenopausal women who had taken tamoxifen for their breast cancer and treated them with either letrozole or a placebo. Letrozole treatment reduced the risk of breast cancer recurrence by over 40%. The study ended early because of overwhelmingly positive results. The drug also prevented metastasis of the cancer to other regions of the body. Results from this clinical study were published in The New England Journal of Medicine in 2003, and two years later the therapy was approved by Health Canada. [12] Later studies suggested that extending treatment with an aromatase inhibitor like letrozole to ten years further increases disease-free survival rates. [13] Another study looked at the effects of adjuvant therapies like letrozole in women of different ages, both premenopausal and postmenopausal. Pritchard found that letrozole favorably impacted women in both groups but was overall more effective in premenopausal women who had been previously treated with tamoxifen. The overarching conclusion from this study was that anti-estrogen treatments like letrozole generally benefit patients when administered any time after the primary treatment. [14]

Pritchard has postulated that women with breast cancer and high levels of the HER-2/neu protein are predisposed to respond more favorably to anthracycline-containing chemotherapy drugs than women with normal HER-2/neu levels. The target of anthracycline drugs is topoisomerase II, and its location in regards to the HER-2 gene on the chromosome is what allows the anthracycline drug to be effective in patients with heavy expression of the HER-2/neu protein. Pritchard demonstrated that women with high levels of HER-2 expression have a better response to the anthracycline containing drugs in a clinical trial. [15] Pritchard's research suggests that the HER-2 gene could be useful as a possible predictor of the adjuvant therapy that is most effective in certain patients. Her study demonstrated ways in which chemotherapy can be tailored to the specific patient. The goal of such tailored therapy is that patients can be spared the toxicity and side effects of drugs that they do not actually need. [16]

Some of Pritchard's most recent research has to do with endocrine therapy combination strategies for the treatment of HR1/HER2–advanced breast cancer in postmenopausal women. The best sequencing for endocrine therapy combination treatment has yet to be determined, but much evidence supports that some combinations help with first-line defense and other combinations work as second-line defense. First-line therapy for advanced breast cancer patients could either be a combination of fulvestrant and anastrozole or palbociclib and letrozole. Combinations of everolimus and exemestane or palbociclib plus fulvestrant are good second-line therapies. With second-line therapy combinations there are some risks for toxicity, which can be controlled by early and regular monitoring. [17]

Pritchard also collaborated on a study that looked at different irradiation approaches as primary therapies for early stage breast cancer patients. Pritchard looked at the outcomes of whole breast irradiation with or without additional nodal irradiation in early-stage breast cancer patients. Patients were either given whole breast irradiation or whole breast irradiation with additional nodal irradiation. The researchers followed up with patients after ten years. There was no significant difference in the rate of survival between the two treatment groups. However, the group treated with additional nodal irradiation did have a lower incidence of recurring breast cancer. [18]

Recent research explores Oncotype DX as a prognostic tool in predicting the likelihood of breast cancer recurrence. Oncotype DX is a genetic recurrence-scoring tool that measures expression of certain genes associated with breast cancer. A higher score indicates a higher chance of recurring cancer. One project, the TAILORx study, uses the Oncotype DX score to gauge the need for adjuvant therapy and to predict the response to such adjuvant chemotherapy treatments. Pritchard was able to confirm Oncotype DX as a useful tool in deciding upon treatment for low-scoring patients. Current results are inconclusive as to Oncotype DX's predictive ability for middle-scoring patients. [19] [20]

Pritchard also explored the effects of hormone replacement therapy (HRT) on women and the potential for developing breast cancer. HRT is usually given to women who are estrogen deficient or menopausal women to lessen their symptoms of menopause. Through her studies of long-term HRT effects, Pritchard discovered there is a 53% higher risk for women developing cancer with a HRT combination of progesterone and estrogen, but only a 34% higher risk in women who just receive estrogen. Other risks include its cardiovascular effects, such as blood clotting, and dense breast tissue, which makes it harder to read a mammogram. Pritchard suggests alternatives to combat estrogen deficiency and menopausal symptoms. Alternatives include Vitamin E, calcium supplements, venlafaxine, clonidine, and diet. She concludes that it may not be as effective, but it does not have the increased risk for breast cancer. [21]

Memberships

Pritchard was a founding member of the Canadian Oncology Society in 1978 and a founding member of the Canadian Association of Medical Oncology in 1988, serving as its president from 1990 to 1992. She served as chair and co-chair of the Ontario Practice Guidelines Initiative's Breast Cancer Site Group between 1990 and 2002. She served on the board of directors for the American Society of Clinical Oncology in 2006. [7]

Awards and honors

In 2005, Pritchard was awarded the O. Harold Warwick Prize by the Canadian Cancer Society for her clinical trials work on breast cancer. [22] In 2015, she was the Scientific Honoree at the 14th Women of Action awards luncheon hosted by the Israel Cancer Research Fund in Toronto. [23] In December 2017, it was announced that Dr. Pritchard has been honoured as a Member of the Order of Canada (CM). [24]

Selected publications

Related Research Articles

<span class="mw-page-title-main">Breast cancer</span> Cancer that originates in mammary glands

Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.

<span class="mw-page-title-main">Anastrozole</span> Chemical compound

Anastrozole, sold under the brand name Arimidex among others, is an antiestrogenic medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used to prevent breast cancer in those at high risk. It is taken by mouth.

<span class="mw-page-title-main">Endometrial cancer</span> Uterine cancer that is located in tissues lining the uterus

Endometrial cancer is a cancer that arises from the endometrium. It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination, pain during sexual intercourse, or pelvic pain. Endometrial cancer occurs most commonly after menopause.

<span class="mw-page-title-main">Tamoxifen</span> Medication

Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men. It is also being studied for other types of cancer. It has been used for Albright syndrome. Tamoxifen is typically taken daily by mouth for five years for breast cancer.

<span class="mw-page-title-main">Aromatase inhibitor</span> Class of drugs

Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone exogenously. They may also be used for chemoprevention in women at high risk for breast cancer.

<span class="mw-page-title-main">Letrozole</span> Breast cancer drug

Letrozole, sold under the brand name Femara among others, is an aromatase inhibitor medication that is used in the treatment of breast cancer.

Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments. An example of such adjuvant therapy is the additional treatment usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to the presence of undetected disease. If known disease is left behind following surgery, then further treatment is not technically adjuvant.

<span class="mw-page-title-main">Exemestane</span> Breast cancer medication

Exemestane, sold under the brand name Aromasin among others, is a medication used to treat breast cancer. It is a member of the class of antiestrogens known as aromatase inhibitors. Some breast cancers require estrogen to grow. Those cancers have estrogen receptors (ERs), and are called ER-positive. They may also be called estrogen-responsive, hormonally-responsive, or hormone-receptor-positive. Aromatase is an enzyme that synthesizes estrogen. Aromatase inhibitors block the synthesis of estrogen. This lowers the estrogen level, and slows the growth of cancers.

<span class="mw-page-title-main">Toremifene</span> Chemical compound

Toremifene, sold under the brand name Fareston among others, is a medication which is used in the treatment of advanced breast cancer in postmenopausal women. It is taken by mouth.

<span class="mw-page-title-main">V. Craig Jordan</span> American/British pharmacologist (born 1947)

Virgil Craig Jordan,, is a scientist with American and British citizenship specializing in drugs for breast cancer treatment and prevention. Currently, he is Professor of Breast Medical Oncology, and Professor of Molecular and Cellular Oncology at the University of Texas MD Anderson Cancer Center, Houston, Texas. Previously, he was Scientific Director and Vice Chairman of Oncology at the Lombardi Comprehensive Cancer Center of Georgetown University. Jordan was the first to discover the breast cancer prevention properties of tamoxifen and the scientific principles for adjuvant therapy with antihormones. More recently his work has branched out into the prevention of multiple diseases in women with the discovery of the drug group, selective estrogen receptor modulator (SERMs). Currently, he plans to develop a new Hormone Replacement Therapy (HRT) for post-menopausal women that prevents breast cancer and does not increase the risk of breast cancer.

Post-chemotherapy cognitive impairment (PCCI) describes the cognitive impairment that can result from chemotherapy treatment. Approximately 20 to 30% of people who undergo chemotherapy experience some level of post-chemotherapy cognitive impairment. The phenomenon first came to light because of the large number of breast cancer survivors who complained of changes in memory, fluency, and other cognitive abilities that impeded their ability to function as they had pre-chemotherapy.

Hormonal therapy in oncology is hormone therapy for cancer and is one of the major modalities of medical oncology, others being cytotoxic chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine system through exogenous or external administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones. Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.

Breast cancer management takes different approaches depending on physical and biological characteristics of the disease, as well as the age, over-all health and personal preferences of the patient. Treatment types can be classified into local therapy and systemic treatment. Local therapy is most efficacious in early stage breast cancer, while systemic therapy is generally justified in advanced and metastatic disease, or in diseases with specific phenotypes.

Antihormone therapy is a type of hormone therapy that suppresses selected hormones or their effects, in contrast with hormone replacement therapy, which encourages hormone activity.

Breast cancer classification divides breast cancer into categories according to different schemes criteria and serving a different purpose. The major categories are the histopathological type, the grade of the tumor, the stage of the tumor, and the expression of proteins and genes. As knowledge of cancer cell biology develops these classifications are updated.

<span class="mw-page-title-main">Nafoxidine</span> Chemical compound

Nafoxidine or nafoxidine hydrochloride is a nonsteroidal selective estrogen receptor modulator (SERM) or partial antiestrogen of the triphenylethylene group that was developed for the treatment of advanced breast cancer by Upjohn in the 1970s but was never marketed. It was developed at around the same time as tamoxifen and clomifene, which are also triphenylethylene derivatives. The drug was originally synthesized by the fertility control program at Upjohn as a postcoital contraceptive, but was subsequently repurposed for the treatment of breast cancer. Nafoxidine was assessed in clinical trials in the treatment of breast cancer and was found to be effective. However, it produced side effects including ichthyosis, partial hair loss, and phototoxicity of the skin in almost all patients, and this resulted in the discontinuation of its development.

A CDK inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), a CDK4/6 inhibitor, in February 2015, for use in postmenopausal women with breast cancer that is estrogen receptor positive and HER2 negative. While there are multiple cyclin/CDK complexes regulating the cell cycle, CDK inhibitors targeting CDK4/6 have been the most successful, with 4 CDK4/6 inhibitors haven been FDA approved. No inhibitors targeting other CDKs have been FDA approved, but several compounds are in clinical trials.

<span class="mw-page-title-main">Palbociclib</span> Medication for HR+ HER2− breast cancer

Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy.

Estrogen deprivation therapy, also known as endocrine therapy, is a form of hormone therapy that is used in the treatment of breast cancer. Modalities include antiestrogens or estrogen blockers such as selective estrogen receptor modulators (SERMs) like tamoxifen, selective estrogen receptor degraders like fulvestrant, and aromatase inhibitors like anastrozole and ovariectomy.

Endocrine therapy is a common treatment for estrogen receptor positive breast cancer. However, resistance to this therapy can develop, leading to relapse and progression of disease. This highlights the need for new strategies to combat this resistance.

References

  1. 1 2 Habib, Marlene (4 April 1997). "New Drug Offers Patients Hope". Brandon Sun. Brandon, Manitoba, Canada. p. 11. Retrieved 2 November 2015– via Newspaperarchive.com. Open Access logo PLoS transparent.svg
  2. ↑ "New drug provides alternative for post-menopausal patients". Lethbridge Herald. Lethbridge, Alberta, Canada. 27 June 2000. p. 10. Retrieved 2 November 2015– via Newspaperarchive.com. Open Access logo PLoS transparent.svg
  3. 1 2 Mahendraraja, Shujanaa (23 July 2014). "Thomson Reuters ranked the top scientific researchers of the world: Meet the 19 U of T scholars on the list". University of Toronto . Retrieved 8 November 2015.
  4. ↑ "The World's Most Influential Scientific Minds 2014" (PDF). Thomson Reuters. 2014. p. 31. Archived from the original (PDF) on 17 November 2015. Retrieved 8 November 2015.
  5. ↑ "Highly Cited Researchers 2015". Thomson Reuters. 2015. Retrieved 2 November 2015.
  6. 1 2 Bitti, Mary Teresa (24 September 2009). "A training ground for biotech leaders". canada.com. Retrieved 8 November 2015.
  7. 1 2 3 4 "Kathleen Pritchard". Toronto, Canada: Ontario Institute for Cancer Research. 7 July 2009. Retrieved 2 November 2015.[ permanent dead link ]
  8. ↑ "Fears of chemotherapy worse than breast cancer diagnosis". Lethbridge Herald. Lethbridge, Alberta, Canada. 19 May 1999. p. 7. Retrieved 2 November 2015– via Newspaperarchive.com. Open Access logo PLoS transparent.svg
  9. ↑ "Hormone replacement carries risk". Medicine Hat Daily News. Medicine Hat, Alberta, Canada. 31 January 2000. p. 13. Retrieved 2 November 2015– via Newspaperarchive.com. Open Access logo PLoS transparent.svg
  10. ↑ "Drug helps prevent recurrence of breast cancer". Lethbridge Herald. Lethbridge, Alberta, Canada. 15 July 2004. p. 6. Retrieved 2 November 2015– via Newspaperarchive.com. Open Access logo PLoS transparent.svg
  11. ↑ "Kathleen Pritchard - Sunnybrook Research Institute". sunnybrook.ca. Retrieved 2016-11-28.
  12. ↑ "Spotlight on Breast Cancer Research: Trial and Success - Sunnybrook Research Institute". sunnybrook.ca. Retrieved 2016-11-28.
  13. ↑ Goss, Paul E.; Ingle, James N.; Pritchard, Kathleen I.; Robert, Nicholas J.; Muss, Hyman; Gralow, Julie; Gelmon, Karen; Whelan, Tim; Strasser-Weippl, Kathrin (2016-07-21). "Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years". The New England Journal of Medicine. 375 (3): 209–219. doi:10.1056/NEJMoa1604700. ISSN   1533-4406. PMC   5024713 . PMID   27264120.
  14. ↑ Goss, P. E.; Ingle, J. N.; Martino, S.; Robert, N. J.; Muss, H. B.; Livingston, R. B.; Davidson, N. E.; Perez, E. A.; Chavarri-Guerra, Y. (2016-11-28). "Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole". Annals of Oncology. 24 (2): 355–361. doi:10.1093/annonc/mds330. ISSN   0923-7534. PMC   3551482 . PMID   23028039.
  15. ↑ Pritchard, Kathleen I.; Messersmith, Hans; Elavathil, Leela; Trudeau, Maureen; O'Malley, Frances; Dhesy-Thind, Bindi (2008-02-10). "HER-2 and topoisomerase II as predictors of response to chemotherapy". Journal of Clinical Oncology. 26 (5): 736–744. doi:10.1200/JCO.2007.15.4716. ISSN   1527-7755. PMID   18258981.
  16. ↑ "Clinical Epidemiology: Take Three - Pritchard - Sunnybrook Research Institute". sunnybrook.ca. Retrieved 2016-11-28.
  17. ↑ Pritchard, Kathleen; Chia, Stephen; Simmons, Christine; McLeod, Deanna; Paterson, Alexander; Provencher, Louise; Rayson, Daniel (January 2017). "Enhancing Endocrine Therapy Combination Strategies for the Treatment of Postmenopausal HR1/HER2– Advanced Breast Cancer". The Oncologist. 22 (1): 12–24. doi:10.1634/theoncologist.2016-0185. PMC   5313264 . PMID   27864574.
  18. ↑ Whelan, Timothy J.; Olivotto, Ivo A.; Parulekar, Wendy R.; Ackerman, Ida; Chua, Boon H.; Nabid, Abdenour; Vallis, Katherine A.; White, Julia R.; Rousseau, Pierre (2015-07-23). "Regional Nodal Irradiation in Early-Stage Breast Cancer". The New England Journal of Medicine. 373 (4): 307–316. doi:10.1056/NEJMoa1415340. ISSN   0028-4793. PMC   4556358 . PMID   26200977.
  19. ↑ Jerzak, Katarzyna J.; Pritchard, Kathleen I. (2016-11-01). "The 21-gene recurrence score assay in node-negative early breast cancer: Prognostic, predictive or presumptuous?". European Journal of Cancer. 68: 173–175. doi:10.1016/j.ejca.2016.08.021. PMID   27768924.
  20. ↑ "A tapestry of clinical trials - SRI Magazine 2016 - Sunnybrook Research Institute". sunnybrook.ca. Retrieved 2016-11-28.
  21. ↑ Pritchard, Kathleen (August 2001). "Hormone Replacement in Women with a History of Breast Cancer". The Oncologist. 6 (4): 352–362. doi: 10.1634/theoncologist.6-4-353 . PMID   11524554.
  22. ↑ "Research Awards: O. Harold Warwick Prize". Canadian Cancer Society. 2015. Retrieved 8 November 2015.
  23. ↑ "Women of Action". Israel Cancer Research Fund. 2015. Retrieved 8 November 2015.
  24. ↑ "The Governor General of Canada".
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