Table 3.
Published medical literature evaluating delays to chemotherapy and patterns of care, with survival outcomes for breast cancer.
| Study | n | Measure | Median (d) | Comparison | HR, p | Notes |
|---|---|---|---|---|---|---|
| Recht, New Engl J Med 1996 | 244 | Breast Conservation to Chemotherapy |
* XRT = 36 Chemo=136 |
Chemotherapy before vs after XRT | LR p=0.07 OS p=0.11 |
LR more common when chemo given first, systemic recurrence when XRT given first. |
| Cold, Br J Cancer 2005 | 352 | Surgery to Chemotherapy getting CMF | Not Given | 1–3;4,5,6–13 wks | p=0.1627 | Danish Breast Cancer Cooperative Group trials |
| 6,065 | Surgery to Chemotherapy getting CMF IV | p =0.1913 | ||||
| 1,084 | Surgery to Chemotherapy getting CEF | p =0.6567 | ||||
| Hershman, Br Cancer Res Treat 2006 | 5,003 | Surgery to Chemotherapy | Not Given** | <1;1–≤2;2–≤3;>3 mos | DSS=1.69 OS=1.46 |
<3 mos NS; HR for >3 mos; Women ≥65 y, 1992–1999, stages I–II; SEER-Medicare |
| Lohrisch, J Clin Oncol 2006 | 2,594 | Surgery to Chemotherapy | Not Given§ | ≤4;>4–8;>8–12;>12–24 wks | OS=1.6 p=0.005 |
HR ≤12 v >12; British Columbia Cancer Agency |
| Sanchez, Br Cancer Res Treat 2007 | 2,782 | Surgery to Chemotherapy | Not Given | <3;3–6;6–9;>9 wks | DFS p=0.26 OS p=0.605 |
Females Stage I, II, IIIa. |
| Yu, BMC Cancer 2013 | 34,097 | Surgery to Chemotherapy | Not Given | Per 4 week delay | DFS=1.16 OS=1.15 |
Meta-analysis of surgery to chemotherapy studies |
| Gagliato, J Clin Oncol 2014 | 6,827 | Surgery to Chemotherapy | Not Given | ≤30, 31–60, ≥61 days | ≥61d lowers DRFS, OS |
Stage I–III, 1997–2011 |
| Chavez-MacGregor JAMA Oncol 2016 | 13,869 | Surgery to Chemotherapy, HR+ | 46‡ | <31, 31–60, 61–90, ≥91 days | DSS=NS | All intervals HR was NS |
| 6,276 | Surgery to Chemotherapy, HER2+ | DSS=NS | All intervals HR was NS | |||
| 4,698 | Surgery to Chemotherapy, Triple negative | HR=1.53 | HR same for DSS & OS (>90d only:Others NS) | |||
| Raphael, Br Cancer Res Treat 2016 | 14 studies | Surgery to Chemotherapy getting AC | Not Given | 4 week interval increase | OS RR= 1.04–1.08 | Study-level meta-analysis of observational studies |
| Yu, Oncotarget 2017 | 667 | Surgery to Chemotherapy, Luminal A | Not Given† | ≤4;4–8;>8 wks | HR=NS | HRs are for ≤8 vs >8 weeks to chemotherapy |
| 328 | Surgery to Chemotherapy, Luminal B | HR=1.93 | ||||
| 270 | Surgery to Chemotherapy, Triple Negative | HR=2.55 | ||||
| 143 | Surgery to Chemotherapy, HER2 Neu | HR=2.41 | ||||
| Abdel-Rahman, Breast 2018 | 3,390 | Surgery to Chemotherapy, HR− | Not Given | <>6 wks | p =0.006 | Pts from 3 clinical trials; <>3 wks NS for all. P values given but no hazard ratios. XRT delays NS. |
| Surgery to Chemotherapy, HR+ | p =0.268 | |||||
| Surgery to Chemotherapy, Overall | p =0.534 |
HR = hazard ratio; XRT = radiotherapy; LR – local recurrence; CMF = cyclophosphamide, methotrexate, 5-fluorouracil; CEF = cyclophosphamide, epirubicin, 5-fluorouracil; wks = weeks; mos = months; DSS = disease specific survival; DFS = disease free survival; DRFS = distant recurrence-free survival; OS = overall survival; AC = doxorubicin, cyclophosphamide; RR = relative risk; NS = not significant; HR −= Hormone receptor negative; HR+ = Hormone receptor positive
Times are between last breast surgery until radiotherapy for the radiotherapy-first group, and until chemotherapy in the chemotherapy-first group.
Chemotherapy received by 47% within 1 month, 37% between months 1–2, 6% between months 2–3, and 10% after 3 months.
Chemotherapy received by 38% ≤4 weeks, 49% >4 to 8 weeks, 8.4% >8 to 12 weeks, and 4.3% >12 to 24 weeks.
Chemotherapy received by 89.6% ≤4 months and 10.4% >4 months from surgery.
Chemotherapy received by 21% within 31 days, 50% 31–60 days, 19.2% 61–90 days, and 9.8% ≥91 days after surgery.
Chemotherapy received by 60% within 4 weeks, and 6.5% after 8 weeks from surgery.