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#Ladyballs

Le Pouls AEEMUM

par Omar Salah Salah

Ladyballs is the provocative term coined by Ovarian Cancer Canada to describe ovaries with the intent of drawing attention to ovarian cancer (1).  The ovaries constitute the core of the female reproductive system whose primary function is to produce oocytes and the supportive hormones, estrogen and progesterone (2). Oocytes are the female germ cells that following fertilization by sperm give rise to the embryo.   Estrogen has major roles in female physiology and in the appearance of sexual characteristics, whereas progesterone is crucial for maintaining pregnancy (2). Ovaries are central for reproduction and for women’s health but they are also prone to disease. 

Epithelial ovarian cancer constitutes 90% of all ovarian cancers (3). It is the deadliest gynecological malignancy in the western world, because the disease often goes undetected until late stages when it is hard to treat (4). The onset of epithelial ovarian cancer is poorly understood and its origins are debated among experts. It is well accepted that it arises either from the fallopian tube epithelium (FTE), the ovarian surface epithelium (OSE) or endometrial tissue (5).  Secretory cells of the FTE are believed to give rise to precursor malignant lesions that offer the earliest glimpses of ovarian cancer (5). The OSE is a single layer of epithelial cells that covers the ovary. During ovulation, the OSE ruptures to release the oocyte and undergo wound repair. It is believed that multiple rounds of rupture and wound repair due to ovulation lead to accumulation of cell damage in the OSE which makes it more prone to transformation into cancer (6). Endometrial explants resulting from endometriosis, an abnormal cellular growth of endometrial cells outside of the uterus, are thought to transform in the pelvic cavity (5).  Irrespective of an origin of cancer in the FTE, OSE or endometrial tissue, the ovary frequently becomes the site of profound tumor growth (5).  Importantly, epithelial ovarian cancer is the primary cause of death from gynecological malignancies and it has multiple sites of origin. 

Ovarian cancer symptoms are vague and often dismissed (7).  The most common symptoms include bloating, difficulty eating, urgency to urinate, abdominal pain and abnormal fullness after eating. While these symptoms are not uncommon, it is the persistence of these symptoms over time that can alert women to this serious underlying disease (7).  Unfortunately, early stages of ovarian cancer are sometimes symptomless and signs start to appear once the tumors grow in size and disease has progressed.

There are no reliable screening methods to detect ovarian cancer at an early stage (8). The diagnosis of ovarian cancer is based on symptoms, a complete pelvic examination, transvaginal ultrasound and blood tests. Unfortunately, non-invasive tests are usually inconclusive and tissue biopsy is the only certain way to confirm the diagnosis (8).

The primary line of treatment for ovarian cancer is debulking surgery, in which surgeons remove as much cancer tissue as possible (9). Most of the time, surgery is either preceded (neoadjuvant) or followed (adjuvant) by chemotherapy. The goal of neoadjuvant therapy is to shrink tumors before surgery, whereas adjuvant therapy aims to eliminate any remaining cancer cells that couldn’t be removed during surgery to avoid cancer recurrence (10). Most of the time, chemotherapy consists of platinum and taxane based drugs that are used in combination. Although 60-80% of patients show a complete response to chemotherapy, they eventually relapse due to chemoresistance and survival is poor (11). The mechanisms by which ovarian tumors become resistant to chemotherapy are poorly understood but may include alterations in drug transport, activation of cell detoxification proteins and increased tolerance for induced DNA damage (11). 

Cancers with high mortality rates are disproportionately underfunded in comparison to those with high survival rates (12). Cancers with high survival rates such as breast and prostate cancer, leave numerous survivors who become advocates for their disease.  The large numbers of survivors are more effective at raising awareness, fundraising and lobbying for more investment into research into their specific neoplasm.  Ovarian cancer prognosis has not improved in more than fifty years, in part, due to low investment in research (13). Approximately 75% of ovarian cancer patients are diagnosed at a late stage and are too sick to be advocates for their disease which hampers efforts to raise awareness and investment in research into ovarian cancer (11, 13).   Breast cancer has a net survival of 87% compared to 44% for ovarian cancer (14). In Canada in 2013, 74 million dollars were invested in breast cancer research, whereas only 1/5 of this amount, 13.8 million dollars, was invested in ovarian cancer research (Fig.1) (15).  

In summary, the ovary is an important organ for female reproduction and health. Even though ovarian cancer was discovered over a century ago, its etiology is poorly understood and remains the deadliest gynecological neoplasm in developed countries. The OSE, FTE and endometrial tissue are accepted sites of ovarian cancer genesis. Ovarian cancer symptoms are very subtle, on their own relatively common, but distinguished by their persistence over time.  As of today, there are no reliable screening tests for ovarian cancer. Surgery remains the best treatment for ovarian cancer. Chemoresistance is still a major treatment obstacle for patients. Underfunding of ovarian cancer hampers research that can advance screening and treatment options.  In the end, every woman should know about ovarian cancer and help raise awareness because ovarian cancer diagnosis shouldn’t be a death sentence. #Ladyballs

Figure 1. Canadian money investment in cancer research during 2013 (15).

References:

  1. Ovarian Cancer Canada. (2017). I’ve got the Ladyballs to talk about it. Retrieved from: http://ovariancanada.org/got-ladyballs?lang=en-CA&_ga=2.47711524.2082285261.1506911651-1890721814.1506442907&_gac=1.39738577.1506604755.CJLdjIf8x9YCFV24wAodmXgINg

  2. Holesh et al., (2017) Physiology-Ovulation. StatPearls. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK441996/

  3. Li S et al., (2017) Identification of Candidate Biomarkers for Epithelial Ovarian Cancer Metastasis Using Microarray Data. Oncology Letters 14.4, 3967-3974. 

  4. Laviolette et al., (2010) 17Beta-Estradiol Accelerates Tumor Onset and Decreases Survival in a Transgenic Mouse Model of Ovarian Cancer. Endocrinology 151, 929-938.

  5. Kurman RJ et al., (2010) The Origin and Pathogenesis of Epithelial Ovarian Cancer- a Proposed Unifying Theory. The American journal of surgical pathology 34, 433-443. 

  6. Annie Ng et al., (2015) Ovary versus fimbria as epithelial ovarian cancer (EOC) source. Nature Reviews Molecular Cell Biology 16, 625-638. 

  7. Kubeček et al., (2017) The pathogenesis, diagnosis, and management of metastatic tumors to the ovary : a comprehensive review. Clinical & Experimental metastasis 34, 295-307. 

  8. Capriglione S et al., (2017) Ovarian cancer recurrence and early detection : may HE4 play a key role in this open challenge. Med Oncol 164, 20-34.

  9. Hanley GE et al., (2017) Risk-reducing Surgery in Women at Low Lifetime Risk of Developing Ovarian Carcinoma. Clin Obstet Gynecol 10.

  10.  Michelle X Liu et al., (2012) Mechanisms of Chemoresistance in Human Ovarian Cancer at a Glance. Gynecology & Obstetrics 2, 1-4.

  11.  Kar-San Ling et al., (2005) Mechanisms Involved in Chemoresistance in Ovarian Cancer. Taiwanese Journal of Obstetrics and Gynecology 44, 209-217.

  12.  Carter AJ et al., (2012) A comparison of cancer burden and research spending reveals discrepancies in the distribution of research funding. Public Health 12, 526.

  13.  Ovarian Cancer Canada. (2017). Demand more ovarian cancer research funding. Retrieved from: http://ovariancanada.org/stories-and-media/feature-stories/2016/demand-more-ovarian-cancer-research-funding?lang=en-CA&_ga=2.18311098.2082285261.1506911651-1890721814.1506442907&_gac=1.122018681.1506604755.CJLdjIf8x9YCFV24wAodmXgINg

  14.  Canadian Cancer Society (2017). Breast cancer- Prognosis and survival for breast cancer. Retrieved from : http://www.cancer.ca/en/cancer-information/cancer-type/breast/prognosis-and-survival/?region=qc

  15. Ovarian Cancer Canada. (2017). Demand more ovarian cancer research funding. Data generated by the Canadian Cancer Research Alliance in 2013: http://ovariancanada.org/stories-and-media/feature-stories/2016/demand-more-ovarian-cancer-research-funding?lang=en-CA&_ga=2.18311098.2082285261.1506911651-1890721814.1506442907&_gac=1.122018681.1506604755.CJLdjIf8x9YCFV24wAodmXgINg

Image de couverture : https://www.health.com/condition/ovarian-cancer/early-signs-ovarian-cancer

*Texte en anglais selon les règles du concours. Les textes du Pouls sont habituellement en français.