Should I get prophylactic mastectomy if I have ovarian cancer and BRCA gene mutations?

About 10-15% of patients with ovarian cancers may have genetic mutation of BRCA1 and BRAC2 genes.  Mutations in these genes predispose women for breast cancer as well.  However, the most appropriate management of breast cancer risk in these patients has not been defined.     

A 2013 study evaluated164 patients had BRCA-ovarian cancer (115 with BRCA1; 49 with BRCA2). Of these 164 patients, 152 developed ovarian cancer prior to BRCA testing (median time to testing, 2.4 years [0.01-55 years]). There were 46 deaths, but none were due to breast cancer. The 5- and 10-year overall survival were 85% (95% confidence interval [CI]= 0.78, 0.90) and 68% (95% CI = 0.59, 0.76), respectively. There were 18 metachronous breast cancer diagnoses.

The conclusion of the study was for women with a BRCA-associated epithelial ovarian cancer, the greatest risk of death was from ovarian cancer and not breast cancer.  Thus,  breast cancer surveillance with mammography and breast-clinical exam are a reasonable alternative to prophylactic bilateral mastectomy.

Reference: Domchek SM, Jhaveri K, Patil S, Stopfer JE, Hudis C, Powers J, Stadler Z, Goldstein L, Kauff N, Khasraw M, Offit K, Nathanson KL, Robson M.  Risk of metachronous breast cancer after BRCA mutation-associated ovarian cancer.  Cancer. 2013 Apr;119(7):1344-8.

New update for recurrent cervical cancer - the role of bevacizumab (avastin)

About 15 to 60% of patients with cervical cancer develop recurrent of their cancer.  Patients with local/central (in the uterus, vagina) locations has potential curative chance with more radical surgery (pelvic exenteration).   Patients with multiple or distant metastases, unfortunately, are difficult to cure.

A recent study presented at the 2013 ASCO meeting (GOG 240) randomized 452 women with recurrent cervical cancer to chemotherapy with or without bevacizumab. Previous platinum-based therapy was administered with RT in 75 and 74 percent of patients, respectively.   Patients who received Bevacizumab (Avastin) has an improvement in overall survival compared to chemotherapy alone (median, 17 versus 13 months, respectively; hazard ration [HR] 0.71, 95% CI 0.54-0.94).

However, Bevacizumab also increases toxicities such as serious (grade 3/4) bleeding (5 versus 1 percent), venous thromboembolic disease (9 versus 2 percent), and the occurrence of gastrointestinal fistula (3 versus 0 percent). However, there was no difference between the study arms in quality of life up to nine months following the start of therapy. The conclusion of the study is bevacizumab has an important role in patients with recurrent cervical cancer.   

Reference: Tewari KS, Sill M, Long HJ, et al. Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: A phase III randomized trial of the Gynecologic Oncology Group. J Clin Oncol 31, 2013 (suppl; abstr 3).

Chemotherapy-induced peripheral neuropathy (CIPN)

Chemotherapy-induced peripheral neuropathy (CIPN) is common especially in patients taking paclitaxel (Taxol) or cisplatin (Platinol).  CIPN may begin weeks to months after the initiation of treatment and often presents with a sensory neuropathy, including numbness and pain. The most common affected part of the body is hand and feet.  Paclitaxel may also cause diffuse aching discomfort in the legs, hips, and lower back, which develop within 1 to 3 days of paclitaxel administration and largely resolve within 7 days.  Although symptoms may resolve after completion of treatment, they are often only partially reversible, and can remain for years.

Recent study assessed efficacy of oral medications on chronic peripheral neuropathic pain by reviewing various published studies.  Seventeen studies comprised of 5,975 subjects, totaling 38 active trial arms evaluating 7 drugs, and 17 drug-dosing combinations met inclusion criteria. Mean pain reduction over placebo ranked highest for duloxetine 120 mg (1.17 95% CI 0.77, 1.58) and pregabalin 600 mg (1.11 95% CI 0.77, 1.45). The indirect treatment comparison showed largest effect size for duloxetine at 120 and 60 mg followed by pregabalin 600 mg. The study conclusion was pregabalin (lyrica) and duloxetine (cymbalta) had the largest beneficial effects for chronic peripheral neuropathic pain.

Just be aware that duloxetine has an FDA black box warning of suicidality.   Therefore, you should ask your doctor if you have depression or other mental disorder.  Pregabalin has no black box warning - at least at this time.

Reference:   
Ney JP, Devine EB, Watanabe JH, Sullivan SD. Comparative efficacy of oral pharmaceuticals for the treatment of chronic peripheral neuropathic pain: meta-analysis and indirect treatment comparisons. Pain Med. 2013 May;14(5):706-19

Severe fatigue during and after chemotherapy

Some of my patients, who are getting or after chemo treatment completion, complain of feeling severe exhaustion.  One patient reported of feeling good in the morning.  But she would get severe fatigue by the time she takes the morning shower.   NCCN defined this Cancer-Related-Fatigues (CRF) as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning.

CRF seems to be common.  60% to 90% of cancer patients report fatigue with the highest rate of CRF occurring in patients undergoing chemotherapy. Although symptoms may improve after treatment, they can persist for months to years after the completion of therapy.  We don’t know the cause of CRF but recent research supports a role for dysregulation in inflammation and hypothalamic-pituitary-adrenal function.

The recommended CRF treatment is to treat possible comorbid medical conditions, including anemia, pain, depression, insomnia and hypothyroidism. However, the relationship between these symptoms is complex, and it is not clear whether treating comorbid symptoms will actually improve fatigue. For example, trials of nonpharmacologic interventions for insomnia that demonstrated improvement in sleep failed to show benefit for fatigue. Nonetheless, it is still important that other primary symptoms are addressed, such as depression.
No medications have been successful in treating CRF.  Psychostimulants, such as methylphenidate, dexamphetamine and modafinil, have not been clearly shown to improve CRF in clinical trials

Antidepressants have also been investigated for the treatment of CRF but showed no clear value in treating CRF. A randomized trial, studying paroxetine versus placebo in patients with cancer undergoing chemotherapy, found no influence on levels of CRF. Open label, pilot trials of bupropion in CRF appear promising, but need further validation. A large, randomized, controlled clinical trial compared donepezil (acetylcholinesterase inhibitor used to treat dementia ) with placebo, reporting no difference in levels of CRF between groups.

Studies on spplements such asL-carnitine, and coenzyme Q10 have been completed and showed no value.  Data from the ginseng trial is under analysis. Guarana is a plant from the Amazon basin used in the United States in energy drinks and weight loss products showed some promises based on a randomized, controlled trial by Brazilian investigators.

Interestingly, exercise may save the day.  Meta-analyses evaluating the effect of a variety of exercise programs on CRF found that physical exercise helped reduce CRF. Effect sizes ranged from 0.18 to 0.37, with the larger effect size in patients who completed treatment.    Common sense strategies such as education about fatigue, teaching self-care or coping techniques, and energy conservation or activity management seem to be effective.

Reference:

Pachman DR, Barton DL, Swetz KM, Loprinzi CL: Troublesome symptoms in cancer survivors: Fatigue, insomnia, neuropathy, and pain.  J Clin Oncol 2012(Oct);30(30):3687-96

 

Can you treat precancer disease of the uterus without surgery?

Uterine cancer is the most common gynecologic cancer in the United States.  There are over 40,000 American women develop this cancer yearly.   The most common types is the endometrial adenocarcinoma.  If you recall from my previous blog, this is mostly due to excess estrogen from obesity.  In a paper by Dr. Trimble, he quoted case control study which suggests a 200-400% increase risk of endometrial uterine cancer with BMI > 25.  BMI >25 means I weigh 160 lb with height of 5feet 6 inches.  I think you know many people are heavier than this BMI and are at risk of uterine cancer.

Before the uterus turns into cancer due to excess estrogen stimulation, the uterine lining thickens (we call it hyperplasia - excess growth).   This is a precancerous stage and usually accompanied by abnormal uterine bleeding.  In postmenopausal women with bleeding, your doctor usually recommend uterine endometrial biopsy.  Once confirmed, the most effective way is hysterectomy.

However, there are patients who are poor candidate for surgery because of poor health (poorly controlled diabetes, COPD, heart disease, etc).   Dr. Trimble reviewed the literatures and recommended the usage of progestin by mouth or intrauterine (using IUD).   Progestin is basically another hormone that is against the estrogen.   In my patients, I strongly recommend weight loss since many of the excess estrogen is produced by fat.

Reference:
Trimble CL, et al.  Management of endometrial precancers.  Obstet Gynecol. 2012; 120: 1160-75

Is cancer contagious?

If my wife has cancer, can I get the same cancer from her?   In general, the answer is no.    In general, cancer is not contagious like infection.   You don't get colon or breast or ovarian cancer just because you are living with a patient with these cancers.  

However, cervical and liver cancer may be infectious indirect way.  Most cervical cancer is transmitted by Human Papilloma viruses (HPV).  HPV are transmitted, usually, by sexual intercourse.    Certain types of liver cancer can arise from liver cirrhosis.  This liver disease may be caused by another virus called Hepatitis C.  Hepatitis C is usually transmitted by exchanging body fluid (sex, blood transfusion, contaminated needles, etc).

Duration of Tamoxifen for breast cancer

Women diagnosed with Estrogen-receptor positive breast cancer benefit from taking additional pill called Tamoxifen.  The usual duration is usually 5 years therapy.    The Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial randomized 12,894 women for 5 versus 10 years of Tamoxifen therapy.   The study found that women who took tamoxifen for ten years had a significantly lower risk of breast cancer recurrence and lower death rate compared to women who took tamoxifen for five years.   However, taking Tamoxifen for 10 years also resulted in a significantly higher incidence of adverse events including endometrial (uterine) cancer, blood clot in the lung, and ischemic heart disease.

Overall, this study recommends the use of tamoxifen for ten years, instead of five years. Patients with a relatively higher risk of recurrence based on their tumor characteristics (ie, pathological node involvement, large tumor size, or high tumor grade) seem to benefit even more.  The study concluded: "For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis"

Reference:
- Dizon DS, et al.  Uptodate. Accessed 5-26-13
- Davies C, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2012