Important guideline update in a very common clinical scenario. Most practitioners prescribe antiresorptive therapy to prevent osteoporosis/osteopenia in the setting of aromatase-therapy inhibitors. Guidelines recommend consideration of bisphosphonate therapy irrespective of endocrine-tumor status.
To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline.
An Expert Panel conducted a systematic review to identify new, potentially practice-changing data.
Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations.
Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients’ risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer.
Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Focused Update
What is the role of bisphosphonates and other bone-modifying agents in adjuvant therapy among patients with breast cancer?
Postmenopausal (natural or induced) patients, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, with nonmetastatic breast cancer for whom a bone-modifying agent is being considered as an adjuvant systemic therapy to reduce the risk of breast cancer recurrence (ASCO’s breast cancer guideline for cisgender [or nontransgender] men recommends that men with early-stage breast cancer should not be treated with bone-modifying agents to prevent recurrence).
Oncology specialists, other health care providers (including primary care physicians, specialists, nurses, social workers, and any other relevant member of a comprehensive multidisciplinary cancer care team), caregivers, and patients.
An Expert Panel was convened to update clinical practice guideline recommendations on the basis of a systematic review of the medical literature.
NOTE. The Panel acknowledges that access to adjuvant bone-modifying agents discussed herein is not universal because of limited reimbursement or availability.
Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities.
The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool8 provides estimates of benefit of adjuvant bisphosphonate therapy and may aid in shared decision making.
Factors influencing the decision to recommend adjuvant bisphosphonate use that should be weighed in the discussion with patients include the patient’s risk of recurrence, the risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy (type: informal consensus; evidence quality: intermediate; strength of recommendation: moderate).
The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline. Many studies initiated bisphosphonate within 3 months of definitive surgery or within 2 months of completion of adjuvant chemotherapy; this is a consensus recommendation. The therapeutic options, listed alphabetically, with the strongest supporting data include:
Patient preference should be factored into the choice of adjuvant bisphosphonate therapy. Access to adjuvant bisphosphonate therapy may currently limit choice of agent depending on jurisdiction (type: evidence-based, benefits outweigh harms; evidence quality: intermediate; strength of recommendation: moderate).
The Panel does not recommend the use of adjuvant denosumab (type: evidence-based, benefits outweigh harms; evidence quality: intermediate; strength of recommendation: moderate).
Two Phase III studies of adjuvant denosumab did not show a consistent reduction of breast cancer recurrence in any subset of patients with early-stage breast cancer. The larger study, D-CARE, did not show improvement in cancer outcomes with use of denosumab.
MammaPrint did not predict distant recurrence, but it did predict patients who may benefit from extended hormonal therapy. We do have breast index, so now we have options. Breast index can predict the possibility of recurrence though by helping to determine the level of risk.
This study confirms what we saw in initial reports showing the addition of pembro increasing the rate of ypathological complete response (ypCR’s) in the neoadjuvant setting for triple-negative breast cancer (TNBC). New data shows a 5% improvement (87 vs 82%) in overall survival (OS) with the quadruplet. Higher gains but at higher cost of toxicity. The fact that adjuvant intraosseous (IO) does not seem to improve outcomes, but neoadjuvant chemo+IO does show intact tumor-immune interactions to create maximum treatment effectiveness is most likely real. Of note, this seems mostly independent of programmed death-ligand 1 (PDL1) status.
Adding Inavolisib to CKD4/6 inhibitor and AI improved progression-free survival (almost doubled 15 vs 7m) but toxicity was higher still in the single digits (hyperglycemia, diarrhea, stomatitis… all less than 6% G3/4).
Well done study showing a 20% decrease in recurrence risk when using dose dense therapy [EC]/D compared to conventional dose [FEC]/D. Sometimes it is worth it to push.
Myth busted. In aggressive breast cancer, no need to start chemotherapy now, ET and CKD4/6 inhibitors are better tolerated with significant progression-free survival (PFS) benefit and same response rate.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
