Radiation Oncology/Breast/Metastatic

Metastatic Breast Cancer

Local Control

ECOG-ACRIN E2108 -- systemic therapy, followed by systemic therapy vs surgery +/-RT
- Randomized. 390 enrolled, 256 patients randomized. Initial systemic therapy 16-32 weeks, if progression, followed. If stable/responded, Arm 1) continued systemic therapy vs Arm 2) surgery +/- RT based on NCCN guidelines. Primary endpoint OS
- 2022 PMID 34995128 -- "Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108)" (Khan SA, J Clin Oncol. 2022 Mar 20;40(9):978-987.doi: 10.1200/JCO.21.02006. Epub 2022 Jan 7.)
  - Outcome: 3-year OS: systemic only 68% vs surgery 68% (NS). Median OS 4.4 years vs 4.0 years. Locoregional progression 40% vs 16% (p<0.001); of the 40%, 20% received palliative surgery or RT
  - Toxicity: QOL measures similar
  - Conclusion: Early locoregional therapy did not improve survival or quality of life

Tata Memorial; India; 2013 (2005-2013) Abstract Link -- "Surgical removal of primary tumor and axillary lymph nodes in women with metastatic breast cancer at first presentation: A randomized controlled trial" (Badwe R, San Antonio Breast Conference Abstract S2-02, 2013)
- Randomized. 350 patients, metastatic breast cancer, status post anthracycline chemotherapy with objective tumor response. Arm 1) loco-regional treatment (lumpectomy or mastectomy and ALND followed by RT) versus Arm 2) No loco-regional treatment. Endocrine therapy as indicated. Median F/U 1.5 years
- Outcome: Median OS LRT 19 months versus No LRT 20.5 months (NS); 2-year OS 41% vs 43%. No difference afer adjusting for prognostic factors
- Conclusion: Loco-regional treatment has no impact on overall survival, and should be reserved for women who need it for palliative reasons

Turkish Study MF07-01 Abstract Link -- "Early follow up of a randomized trial evaluating resection of the primary breast tumor in women presenting with de novo stage IV breast cancer; Turkish study (protocol MF07-01)" (Soran A, San Antonio Breast Conference Abstract S2-03, 2013)
- Randomized. 278 patients, metastatic breast cancer. Arm 1) loco-regional therapy (mastectomy or lumpectomy + radiation and SNB/ALND) before initiating systemic therapy versus Arm 2) No loco-regional treatment, systemic therapy only. Bone-only 46%; no bone 29%, both bone and other 25%. Median F/U 1.7 years.
- Outcome: 4.5 year OS LRT 35% versus No LRT 31% (NS). Bone-only subgroup mean OS 3.2 years versus 2.7 years (NS); solitary bone only disease statistically significant (numbers not given)
- Conclusion: Overall survival similar; but patients with solitary bone metastases had a survival benefit

Hawaii; 2009 PMID 19876731 -- "Loco-regional treatment in metastatic breast cancer patients: Is there a survival benefit?" (Ly BH, Breast Cancer Res Treat. 2009 Oct 30. [Epub ahead of print])
- Literature review. 13 studies evaluating loco-regional treatment (surgery, or surgery + RT, RT)
- Outcome: Median OS no surgery 12-28 months vs. surgery 25-42 months; 3-year OS 17-79% vs. 28-95%
- Conclusion: Possibility of surgery and/or RT following induction should be left to individual practice

Shrewport, USA; 2014 PMID 25243101 -- "Radium-223 dichloride bone-targeted alpha particle therapy for hormone-refractory breast cancer metastatic to bone." (Takalkar A, Exp Hematol Oncol. 2014 Sep 8;3:23. doi: 10.1186/2162-3619-3-23. eCollection 2014.)
- Case report. 44 female, ER+, hormone refractory/chemotherapy refractory
- Outcome: Improvement in bone pain, decrease in tumor markers, mixed response by PET
- Conclusion: Ra-223 dichloride can be safely administered in breast cancer with prostate cancer dosing

Sheffield Research Centre, UK; 2014 PMID 24728613 -- "A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease." (Coleman R, Breast Cancer Res Treat. 2014 Jun;145(2):411-8. doi: 10.1007/s10549-014-2939-1. Epub 2014 Apr 13.)
- Phase IIA, nonrandomized. 23 breast cancer patient, progressive bone-dominant disease, not candidate for further endocrine therapy. Radium-223 (50 kBq/kg IV) every 4 weeks x 4 cycles
- Outcome: significant reduction in urinary N-telopeptide and bone ALP. By CT, 41% metabolic response rate at week 17
- Toxicity: Safe and well tolerated. Grade 3-4 primarily anorexia (13%), bone pain (9%), and bone marrow suppression. No patient discontinued due to toxicity
- Conclusion: Radium-223 shows biological activity in advanced breast cancer

Turkey (2003-2005) -- Zoledronic acid + RT 30/10 vs. Zoledronic acid + RT 15/5
- Randomized. 100 patients, at least one bone metastasis, life expectancy >6 months. Excluded pathologic fractures, prior RT to that area, prior treatment with zoledronic acid, brain mets. Zoledronic acid 4 mg Q28 days, starting day 1 of RT. Used objective measure (MRI, bone scan) and subjective end points (pain, analgesic score, visual analog score)
- 2009 PMID 19484483 -- "Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study." (Atahan L, Support Care Cancer. 2009 May 31. [Epub ahead of print]). Minimum F/U 6 months
  - Outcome: No difference in time-to-first skeletal event, rate of first-skeleta-event, time-to-response, rate of response, or duration of response. Higher satisfaction in shorter 15/5 arm
  - Conclusion: Concomitant use of zoledronic acid and RT safe