The new guidelines provide the following specific recommendations on how to manage gynecological side effects related to treatment received by women with breast cancer.
Treatment of vasoconstriction symptoms such as hot flashes
Hormone therapy is usually contraindicated in patients with hormone-positive breast cancer, so these patients should be treated with selective 5-hydroxytryptamine reuptake inhibitors (SSRIs), SNRIs (5-hydroxytryptamine-norepinephrine reuptake inhibitors) or gabapentin for vasoconstriction symptoms such as hot flashes.
SSRI: Can be safely used to treat hot flashes in some women with breast cancer and does not increase the risk of disease recurrence in women who become pregnant during breast cancer treatment.
SNRI: For patients treated with tamoxifen, SNRIs are more effective than SSRIs because the former avoids potential interactions. Randomized clinical trials have shown that low-dose (75 mg) venlafaxine (SNRI) significantly relieves symptoms of hot flashes in patients treated for breast cancer.
Gabapentin: Usually an anticonvulsant drug used to control neuropathic pain in breast cancer patients, but small doses of gabapentin also help relieve vasoconstriction symptoms and improve sleep quality. The similar drug to gabapentin, pregabalin, also has beneficial effects similar to those of colistin.
None of these drugs have been approved for hot flashes in the United States until now.
Prevention of bone loss and high risk of fracture
Given that chemotherapeutic agents, ovarian inhibitors, and aromatase inhibitors can cause bone loss and increase the risk of fracture, bisphosphonate therapy should be considered in patients with C2.0 ≤ T value ≤ C1.5 and is strongly recommended for patients with a T value < C2.0 and a 10-year risk of major fracture > 20%, or a 10-year risk of hip fracture > 3%. Zoledronic acid is the best choice among the bisphosphonates, and although raloxifene is usually well tolerated, there are adverse effects in the form of vasoconstriction symptoms. Patients who have experienced significant changes in bone loss risk due to drug therapy (e.g., premenopausal women treated with aromatase inhibitors) should be monitored annually, and vitamin D levels should also be tested in patients with breast cancer.
Relief of severe vaginal dryness
Up to 40% of breast cancer patients have severe vaginal dryness, but the safety of commonly used topical hormonal agents such as creams, suppositories and vaginal rings has not been proven.
Non-hormonal vaginal moistening agents should be preferred in this group of patients, with short-term use of hormonal agents if non-hormonal medications fail. Testosterone supplementation (patches or creams) still lacks sufficient safety data to support it.
Choice of contraceptive methods
Suitable contraceptive methods for breast cancer patients include barrier methods, copper-containing IUDs, and sterilization. Hormonal methods are not suitable for breast cancer patients and are even risky for women with cancer-free survival ≥5 years.
The exception may be the levonorgestrel intrauterine release system, as systemic absorption of levonorgestrel is rare. However, comprehensive studies on the long-term breast cancer risk of this system are lacking, and its use can only be determined on a patient-by-patient basis.
Pregnancy and fertility issues while on treatment
A recent Meta-analysis cited in the new guidelines suggests that pregnancy in breast cancer patients while on treatment does not increase the risk of breast cancer recurrence or death (Eur. J. Cancer 2011;47:74-83). However, chemotherapy impairs fertility, and tamoxifen treatment for 5 years can reduce ovarian reserve function in women, thus making pregnancy difficult for many women of childbearing age after treatment, and patients should be advised to consult about fertility issues at diagnosis in order to prepare in advance.
In vitro fertilization (IVF) with frozen embryos is the best option to preserve fertility, however, some physicians recommend natural cycle (non-stimulated) IVF due to concerns that ovarian stimulation can lead to breast cancer cell proliferation.
It is unclear whether ovarian suppressants have a fertility-preserving effect. Studies have shown that tamoxifen has promise as an ovarian stimulant for the treatment of impaired fertility due to breast cancer treatment.
Although letrozole as an aromatase inhibitor cannot be used in the treatment of premenopausal breast cancer patients, it can be used as a fertility promoting agent in combination with gonadotropins.
Uterine evaluation
For postmenopausal patients treated with tamoxifen without evidence of vaginal bleeding, the new guidelines do not recommend routine endometrial biopsy and uterine ultrasound because ultrasound has been associated with an increased rate of false positives leading to unnecessary invasive diagnostic tests. However, in patients with vaginal bleeding, endometrial evaluation such as biopsy and subsequent examination for possible uterine structural abnormalities is necessary.