Salvador Oscar Rivero Boschert, Jose Joaquin Anguilar-Ramirez, Gregory Lip.
Response/Recommendation: Hormonal therapy used in cancer management, like tamoxifen, increases the risk of venous thromboembolism (VTE) in patients undergoing orthopaedics procedures. We suggest they should be suspended at least 7 days before surgery, a degree of individualization of approach is needed based on risk factors and clinical settling (type of cancer, etc.).
Strength of Recommendation: Weak.
Rationale: Cancer patients have a hypercoagulable state due to the presence of all components of Virchow’s triad. There is evidence of platelet activation along with elevated levels of inflammatory cytokines (vascular endothelial growth factor, tissue factor), tumor mass effect compressing adjacent veins, and damage to the endothelium1.
The rate of VTE in orthopaedic oncology patients has been reported to be between 1% and 28%1.
Following orthopaedic lower limb surgery, pulmonary embolism (PE) are less likely to occur in association with a deep venous thrombosis (DVT) when patients receive prophylaxis with an anticoagulant agent (8% vs. 42%)1.
Hormonal therapies are a mainstay of treatment for prostate and breast cancers. Androgen deprivation therapies, which include gonadotropin-release hormone agonists, oral antiandrogens, and estrogens, have also been reported to increase the risk of VTE2.
In the case of androgenic Hormones such as testosterone and methyltestosterone (used for the treatment of hypogonadism in men and advanced breast cancer in women), and oxymetholone (used for the treatment of cancer-associated anemia), the literature has not demonstrated an association between perioperative VTE events and androgenic hormone use3.
The use of selective estrogen receptor modulators (SERM), such as tamoxifen, is a known risk factor for VTE, namely DVT and PE4. Indeed, tamoxifen is a risk factor for VTE, and the estimates of the risk ratio for VTE, ranging from 1.3 to 7.02.
Nevertheless, there is a paucity of information in the literature about the management of tamoxifen in this population, with merely a suggestion that tamoxifen should be stopped as the risk of developing VTE during the perioperative period4.
A consensus of the Mayo clinic indicates that we should continue SERM before and on the day of surgery if taken for breast cancer prevention or treatment but consider potential for increased wound complication and VTE risk if continued. If SERM are taken for other indications and additional patient or surgery-specific risk factors for VTE are present, we should stop SERM at least 7 days before surgery3. Thus, a degree of individualization of approach is needed.
It is imperative to balance between the continuous cytostatic effect, by continuing tamoxifen; against the reduction of VTE risk, by stopping tamoxifen for a finite period perioperatively. The half-life elimination of tamoxifen is between 5 and 7 days4.
The National Institute for Health and Care Excellence (NICE) guidelines stipulate that tamoxifen may need to be stopped for up to 6 weeks prior to elective surgery, without further details on risk stratification nor specification of the duration of stopping tamoxifen4.
- Lex JR, Evans S, Cool P, Gregory J, Ashford RU, Rankin KS, et al. Venous thromboembolism in orthopaedic oncology: risk factors, incidence, and prophylaxis. The Bone & Joint Journal. 2020 Dec 1;102-B(12):1743–51.
- Giustozzi M, Curcio A, Weijs B, Field TS, Sudikas S, Katholing A, et al. Variation in the Association between Antineoplastic Therapies and Venous Thromboembolism in Patients with Active Cancer. Thromb Haemost. 2020 May;120(05):847–56.
- Pfeifer KJ, Selzer A, Mendez CE, Whinney CM, Rogers B, Simha V, et al. Preoperative Management of Endocrine, Hormonal, and Urologic Medications: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement. Mayo Clinic Proceedings. 2021 Jun;96(6):1655–69.
- Nicola A, Crowley M, See M. A novel algorithm to reduce VTE in peri-operative patients on tamoxifen. The Breast. 2021 Aug;58:88–92.