Reproductive Cancers

Last post on endocrine pathophysiology! This post will cover prostate, cervical, uterine, ovarian and breast cancers. (Yeah, breasts aren't technically a part of the reproductive system, but it affects so many people. Also unfortunately we ran out of time to cover testicular cancer, so guys kinda get neglected a bit >_>)

Prostate Cancer

There are two somewhat related conditions affecting the prostate that you should know: benign prostatic hyperplasia (BPH) and prostate cancer. Benign prostatic hyperplasia is, as the name states, benign. The prostate enlarges from the centre out, forming nodules around the urethra that can block the flow of urine, but these nodules do not progress to cancer. Prostate cancer, on the other hand, is cancer (!). It is the second most common cancer in men (the most common being lung cancer). In advanced stages, it can metastasise to the lymph nodes, liver, lung, bone and adrenal glands.

Symptoms of BPH are mainly related to urinary retention. If untreated, urinary retention can progress to cystitis (inflammation of the bladder), bladder stones and kidney damage. BPH can be treated with medications such as anti-androgen drugs (androgen causes the prostate to grow, so depriving it of androgens causes prostate shrinkage) and α-adrenergic blockers which help to relax the bladder neck. Sometimes surgery may have to be performed, but this is relatively infrequent.

Prostate cancer, despite having similar symptoms to BPH, is obviously a bit nastier, considering that it can metastasise. It's unknown why prostate cancer develops, but age and genetics may have a role. Prostate cancer can be detected by testing for prostate-specific antigen (PSA), though as PSA levels are also elevated in BPH and infection, this needs to be taken in consideration along with a digital rectal exam. To definitively confirm a diagnosis of prostate cancer, a biopsy can be taken, and the cancer can be graded on the Gleason score according to how bad it is.

How can prostate cancer be treated? If it isn't too bad (low Gleason score), just keeping an eye out for further issues might be enough. Otherwise, the prostate can be destroyed by surgery or radiation, including brachytherapy, which is essentially the insertion of radioactive implants into the prostate. GnRH agonists that desensitise GnRH receptors, as well as androgen antagonists, may also be helpful in shrinking the size of the prostate. Sometimes this might be done before surgical removal.

Cervical Cancer

Cervical cancer tends to develop at a relatively young age- around 35 years old for early stage disease (in situ carcinoma). Prior to this early stage, there is dysplasia of the squamous cells at the external os, which can be picked up on a routine Pap smear. Symptoms do not appear until much later. It takes 5-10 years for cervical cancer to become invasive, and even then, it's only at the later stages of invasive cancer that you start to see spotting and watery discharge, and maybe anaemia and weight loss in more severe cases. If detected early, however, five-year survival is almost 100%, which is why pap smears are so important.

Cervical cancer is linked to sexually transmitted infections such as HPV (human papilloma virus), and thus the risk increases the more sexual partners you have. Some strains of HPV can be prevented with anti-vaxers' favourite vaccine *cough.* (The HPV vaccines on the market are Gardasil and Cervarix, but Gardasil's a lot more commonly used as it protects against 4 strains as opposed to Cervarix's 2 strains. I've heard that they're developing a new vaccine against 9 strains of HPV, though.) Although five-year survival rates are pretty damn good, do bear in mind that a positive pap smear can be scary and stressful, and if it develops into cancer, you may have to go through all of the surgery and radiation and all that.

Uterine Cancer

Carcinoma of the uterus tends to develop at an older age: around 55-65 years of age. Unfortunately, there is no screening test for this, so most women with the condition only find out when they get unexpected vaginal bleeding (which is pretty damn unexpected given that most women this age have gone through menopause). If uterine cancer is suspected, it can be confirmed with a biopsy of the endometrium.

In women that have gone through menopause, fat cells still continue to produce oestrogen. There is, however, no opposition to this oestrogen, so the oestrogen continues to stimulate the endometrium. This may lead to hyperplasia (growth of extra cells) and then dysplasia. (You can review this earlier post if you don't understand what the terms mean.) Also bear in mind that postmenopausal women obviously aren't menstruating, so they don't get a chance to get rid of these dysplastic cells.

Treatment of uterine cancer involves the main staples: surgery (hysterectomy in this case) and radiation. Chemotherapy may also be warranted if the cancer has spread to the lymph nodes. If the cancer is confined to the uterus, however, survival rates are pretty good: 90% after five years.

Ovarian Cancer

Ovarian cancer is much rarer, and thank goodness for that because prognosis is so poor (five-year survival of only around 20%). It mainly affects peri- and post-menopausal women. At early stages it is asymptomatic, but later on it can cause bladder and bowel problems.

Unfortunately, ovarian cancer cannot be tested for, but there are some risk factors to keep in mind. A personal or family history of breast, ovarian, endometrial, prostate or colon cancer can increase risk, as can carrying mutations in the BRCA1 or BRCA2 genes (genes that regulate the cell cycle, DNA repair and apoptosis). It seems that risk is also increased by ovulation, as oral contraceptive users have a lower risk of ovarian cancer, but that has still not been determined.

In women that have several risk factors (personal or family history, gene mutations, breast cancer before age 50), a prophylactic oophorectomy (removal of the ovaries) may be performed. Obviously hardly anyone knows if they have a gene mutation or not, and given that the prevalence of mutations is only around 1 in 800 for the general population, people are rarely tested. Ashkenazi Jews may want to consider testing, however, as BRCA1/2 gene mutations are much higher among them: around 1 in 50 carry a mutation.

Treatment for ovarian cancer involves all the usual stuff: surgery, radiation and chemotherapy. Palliative care was also mentioned in the lecture, probably because of the high mortality rate.

Breast Cancer

Breast cancer is pretty common. Chances are, you know someone, or know someone who knows someone, who's had breast cancer. The lifetime risk for most women is 1 in 9, unless they have mutations in the BRCA1/BRCA2 genes, in which case their lifetime risk is a whopping 1 in 2. Women with mutations in these genes are also more likely to develop breast cancer earlier than those without the mutation. Other risk factors for breast cancer include a family history of breast cancer and delayed childbirth. Some women with a very high risk of breast cancer (i.e. strong family history and BRCA mutations) may decide to have a prophylactic mastectomy.

As you are probably aware, mammograms are pretty useful for diagnosing breast cancer. Biopsies can also give a more definitive diagnosis. Treatments involve the standard surgery, radiation and chemotherapy, but if the cancer, like 80% of breast cancers, is oestrogen-receptor positive, then there are other drugs that can help. One of the more commonly-used drugs is Tamoxifen, which is an oestrogen antagonist, but aromatase inhibitors can also help.

And that's it! Good luck on the test this Thursday!