Table 5 Sources of evidence to estimate the natural history of the disease

From previous economic evaluations

 Skedgel et al. (2013) [21]

Disease-free to recurrence

Proportion local recurrence/recurrence

'Instant' conversion from local to distant

Side effects

Rate of nausea |vomiting (grades 3 + 4)

Rate of febrile neutropenia

Rate of CHF

Relative mortality risk |CHF

Rate of AML/MDS

Relative mortality rate |AML/MDS

Relative risk of cardiotoxicity |conTZ

Relative risk of cardiotoxicity |seqTZ

Recurrences from previous economic evaluations [71,72,73]. Adverse side-effects from previous trials [36, 37]

40 years

50 years

60 years

70 years

80 + years

Patients aged > 70 years account for 16% [36]

Patients aged > 60 years account for 16.3% [37]

From randomised controlled trials

 Naeim et al. (2005) [19] and Naeim et al. (2005) [18]

Odds reduction of 10-year mortality

Disease-free to death

Adjuvant Chemo CMF

Adjuvant Chemo AC

Adjuvant Tamoxifen

Adjuvant Chemo CMF + Tamoxifen

Adjuvant Chemo AC + Tamoxifen

Background non-cancer mortality from United States life tables 1997 [74];

45 years

65 years

75 years

85 years

Age-specific mortality from 0 to 100 years

 Sen et al. (2014) [20]

Disease-free to recurrence no RT

Disease-free to recurrence + RT

Recurrence to metastasis

Metastasis to death

Clinical trial [29]

70, 75, and 80 years

 > 70 years

 Ward et al. (2020) [22] and Ward et al. (2019) [23]

Cumulative incidence

Disease-free to death

Overall survival

Death from 2^nd cancer

Disease-free to progression

Ipsilateral breast tumours recurrence

Contralateral breast cancer

Distant metastasis

Side effects

Osteopenia requiring bisphosphonate

Bone fracture

Deep vein thrombosis

Fibrosis/soft-tissue necrosis

Hot flashes

Arthralgia

Radiation dermatitis, acute grade 3

Clinical trials [23, 29,30,31,32,33,34,35]

70 years or older

70 years [29]

 > 65 years [30]

65.7 years [31]

57 years [32]

Not reported [33]

Desch et al. (1993) [24]

Disease-free to progression

First recurrence

Clinical trials [38, 39]

60 years

65 years

70 years

75 years

80 years

48 years [38]

Not reported [39]