You may consider answering the following multiple choice questions before reading the information provided. The answers are given at the bottom of the page.
Q1: All of the following regarding aromatase inhibitors are correct except
1. Unlike tamoxifen, AI’s are associated with an increased risk of endometrial cancer.
2. AI’s have been shown to reduce bone density, and increase the risk of fractures.
3. Aromatase inhibitors are not indicated in premenopausal women.
4. The musculoskeletal symptoms associated with the AI’s are transient.
Q2: Which of the following statements regarding tamoxifen is correct?
1. Compared with AI’s, tamoxifen has been associated with a decreased risk of venous thromboembolic events.
2. Similar to AI’s in post menopausal women tamoxifen increases the risk of bone loss and osteoporosis.
3. In post menopausal women tamoxifen has shown better efficacy than inhibitors.
4. Tamoxifen may be associated with an increased risk of ischemic cereborvascular complications.
Q3: All of the following statement regarding management of side effects of hormonal therapy are correct except
1. Vaginal bleeding is a warning sign for possible endometrial caner or pathology in postmenopausal women on tamoxifen.
2. Fluoxetine is the “selective serotonin reuptake inhibitors (SSRI)” of choice for the management of hot flushes in women taking tamoxifen.
3. Estrogen replacement therapy is contraindicated in women with ER/PR positive breast cancer for managing hot flushes and bone loss.
4. Gabapentin is an active agent for the management of tamoxifen related hot flushes.
Q4: All of the following statement regarding bone health in women taking hormonal therapy are correct except
1. Periodic bone density examination is recommended in postmenopausal women taking AI’s.
2. A bisphosphonate should be considered in all women with osteoporosis.
3. Non-pharmacologic intervention including weight-bearing exercise, smoking cessation, limitation of alcohol, and daily supplemental calcium and vitamin D is routinely recommended in women taking AI’s irrespective of bone density.
4. Raloxifene is a treatment of choice in women with breast cancer and osteoporosis.
Adjuvant hormone therapy in women with estrogen/progesterone receptor positive early-stage breast cancer reduces the risk of both recurrence and mortality.
Premenopausal Women
· 5 years of tamoxifen represents current standard adjuvant hormone therapy.
· Suppression of ovarian function by oophorectomy or LHRH agonist is another effective therapeutic option.
Postmenopausal Women
· Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane are superior to 5 years of adjuvant tamoxifen.
· Some duration of AI therapy is recommended -if continuouss therapy is not chosen,a switch strategy after 2-3 years of tamoxifen may be utilized.
· Aromatase inhibitors are not indicated for premenopausal women.
· Third-generation AI’s have shown a more favorable overall risk-benefit profile than tamoxifen.
· Potential benefits of the AI’s include less frequent gynecologic, cerebrovascular, and thromboembolic adverse events; greater disease-free survival; and lower rate of tumor recurrence.
Adverse Effects
· Data is available from placebo-controlled trials of tamoxifen, head-to-head comparisons of tamoxifen versus AI's given up-front or as sequential therapy, and placebo-controlled trials of AI's in the extended adjuvant setting.
· Although the frequency of specific adverse effects differs between tamoxifen and aromatase inhibitors, the overall quality of life scores aresimilar
· Compared to placebo, neither tamoxifen nor AI's appear to exert a negative effect on overall quality of life.
The following represent important possible side effects observe of adjuvant hormonal therapy.
Hot Flushes
· Hot flushes represent a common side effect of both tamoxifen and AI's
· The reported frequency of hot flushes varies from 32% to 58%.
· Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, paroxetine, venlafaxine, and citalopram, may reduce hot flash frequency and severity.
· In patients with the CYP2D6 genotype, SSRIs and other drugs inhibiting CYP2D6, may alter the effectiveness of tamoxifen.
· Venlafaxine interacts less with CYP2D6 and is First choice Gabapentin, also reduces hot flashes and is preferable to SSRI's in women taking tamoxifen.
Sexual Dysfunction
· Difficulties with sexual functioning represent a common side effect
· AI's are associated with more vaginal dryness ,dyspareunia, and loss of libido compared to tamoxifen.
· For treating vaginal dryness and dyspareunia, water-based lubricants and moisturizers (Replens®), may be considered
· Although systemic absorption is likely minimal, vaginal estrogen creams should probably be avoided in such women as much as possible.
Musculoskeletal Symptoms
· Arthralgias occur more commonly with the AI's than with tamoxifen.
· In clinical trials the incidence varies from 18% to 36%, but may be over 50%
· Musculoskeletal symptoms are manageable with lifestyle changes, including exercise and pharmacologic approaches such as acetaminophen and non-steroidal anti-inflammatory drugs.
· Symptoms may be transient and usually resolved at the end of therapy
Bone Loss
· AI's increase bone turnover, reduce bone density, and increase the risk of fracture
· Tamoxifen has a protective effect on bone density in postmenopausal women.
· When five years each of tamoxifen and anastrozole were compared in a randomized trial, the cumulative incidence of reported fractures was 11% in the anastrozole group and 7.7% in the tamoxifen group (P < .0001).
· Bone density should be measured at baseline, and periodically (1-2 years) for the duration of therapy.
· Non-pharmacologic recommendations include weight-bearing exercise, smoking cessation, limitation of alcohol intake, and both 1200 mg of elemental calcium, and 800 IU of vitamin D daily. .
· National guidelines suggest that women with T-scores lower than -2.5 should also receive a bisphosphonate in addition to calcium and vitamin D
· Use of a bisphosphonate should also be considered for women with bone densities between -1.5 and -2.5 with other associated risk factors for osteoporosis.
· Despite their beneficial role in bone health- estrogen or raloxifene therapy are contraindicated in women with a history of breast cancer
Endometrial Cancer
· The estrogenic activity of tamoxifen on endometrial tissue increases the risk of both benign and malignant uterine pathology
· The increased risk of endometrial cancer with tamoxifen is mostly in women over the age of 50
· A meta-analysis of 32 published randomized placebo controlled trials with tamoxifen therapy revealed a risk ratio of 2.7 for endometrial cancer.
· An increased incidence of uterine sarcoma, particularly malignant mixed mullerian tumors has also been noted
· AI's unlike tamoxifen, have not been associated with increases in endometrial cancer.
· An annual gynecologic examination should be performed in women taking tamoxifen.
· Vaginal bleeding on tamoxifen represents a warning sign for possible endometrial hyperplasia or neoplasm in postmenopausal women.
· Pelvic ultrasound with endometrial biopsy should be performed in such post-menopausal women with vaginal bleeding.
Cardiovascular Events
· Tamoxifen is associated with an increased risk for venous thromboembolic disease particularly in women receiving concomitant chemotherapy.
In a pooled analysis of 13 trials involving 20,878 women, the risk of pulmonary embolism, deep venous thrombosis, and superficial phlebitis was increased 2-3 in those on tamoxifen and 11- 15 x in those on tamoxifen plus chemotherapy.
· Tamoxifen may also be associated with an increased incidence of stroke.
In trials, comparing AI's to tamoxifen, AI' s were associated with a decrease risk of both venous thromboembolic events and ischemic cerebrovascular events.
In other studies, AI's have also been associated with a slightly increase in the risk of ischemic cardiovascular disease/MI compared to tamoxifen, AI's may adversely affect lipid values but to date placebo-controlled trials have provided no conclusive evidence of increased morbidity or mortality.
Multiple choice question answers:
Q1: Answer: 1
Q2: Answer: 4
Q3: Answer: 2
Q4: Answer: 4
