Physical activity, risk of death and recurrence in breast cancer survivors: A systematic review and meta-analysis of epidemiological studies

Figures & data

Figure 1. Selection process of eligible trials for inclusion in review.

Table I. Characteristics of included studies.

First author (trial name), country, design	N Sample and outcomes, years diagnosed and follow-up duration	Sample characteristics	Treatment, disease stage and HR status data	Physical activity (PA) assessment details
Studies including pre-diagnosis lifetime recreational PA analysis only:
Friedenreich (2009), Canada, Prospective cohort follow-up of case-control study	N = 1225 A-C death = 341 BC-R death = 223 Recurrence = 327^a 1995–7, Recurrences min follow-up = 8.3 y Death min follow-up: 10.3 y	Mean = 56 (± 12.1) y Postmenopausal = 62% Mean BMI = 27.4 (± 5.7) Race = NR Family history = 18.4%	Chemotherapy = 35.6% HT/Tamoxifen = 38.6% Stage 0 = 9% Stage I = 42.3% Stage II = 39.8% Stage III = 8.8% HR-status = NR	Interviewer-administered questionnaire given median 3.4 mo after diagnosis. Pre-diagnosis PA (occupational, household and recreational) performed throughout entire lifetime.
Dal Maso (2008) (PACE), Italy, Prospective cohort follow-up of case-control study	N = 1453 A-C death = 503 BC-R death = 398 Recurrence = NR 1991–4, Median follow-up = 13 y	Age < 55 = 47.5% Age ≥ 55 = 52.5% Menopausal status = NR BMI < 25 = 56% BMI 25–< 30 = 32% BMI ≥ 30 = 12% Caucasian = NR Family history = NR	Chemotherapy = NR HT/Tamoxifen = NR Stage I = 32.7% Stage II = 44.2% Stage III–IV = 13.3% ER+/PR+ = 41.5% ER+/PR- = 6.3% ER-/PR- = 10.1% ER-/PR+ = 3.6%	Interview-administered questionnaire taken ≥ 1 y pre-diagnosis. PA at work and in leisure time assessed at various ages over lifetime in h/wk at age 15–19, 30–39 and 50–59 y.
Studies including both lifetime and more recent recreational PA analysis:
Cleveland (2012) (LIBCSP), USA, Prospective cohort follow-up of case-control study	N = 1508 A-C death = 196 BC-R death = 128 Recurrence = NR 1996–7, Mean follow-up = 5.6 (range = 0.2–7.4) y	Mean age = 59y Menopausal status = NR Mean BMI = 26.5 Caucasian = 94% Family history = 20.4%	Chemotherapy = NR HT/Tamoxifen = NR Stage 0 = 15.5% Invasive breast cancer = 84.5% ER+ = 73.3% PR+ = 64.3%	Interviewer-administered questionnaire completed “shortly after diagnosis”. Pre-diagnosis recreational PA for ≥ 1 h/wk for ≥ 3 mo in any year over entire lifetime. PA assessed over time periods: lifetime (h/wk from menarche to diagnosis) and recent PA (< 10 y pre-diagnosis).
Keegan (2010) (BCFR), USA, Canada and Australia, Prospective cohort study	N = 3833 A-C death = 623 BC-R death = NR Recurrence = NR 1991–2000, Median follow-up = 7.8 y	Age 40–49 y = 32% Age ≥ 50 y = 41% Menopausal-status = NR BMI < 25 = 53% BMI 25–29.9 = 26% BMI ≥ 30 = 17% Non-Hispanic white = 75% Family history = NR	Chemotherapy = 49% HT/Tamoxifen = 39% Stage = NR ER+ = 65% PR+ = 63%	Self-administered questionnaire completed a mean 19.2 mo after diagnosis. Pre-diagnosis lifetime recreational PA at ages 12–17 y, 18–24 y, 25–34 y, 35–44 y, 45–54 y, and ≥ 55 y and during 3 y pre-diagnosis (recent PA). Recreational PA, including moderate exercise activities or sports and strenuous exercise activities or sports.
West-Wright (2009) (CTS), USA, Prospective cohort follow-up of a prospective cohort study	N = 3539 A-C death = 460 BC-R death = 221 Recurrence = NR 1995–6 to 2004, Median follow-up = 4.3 y	Mean age = 58.9 (± 12) y Menopausal status = NR BMI < 25 = 55.0% BMI 25–29 = 27.5% BMI ≥ 30 = 13.2% White = 89.7% Family history = NR	Chemotherapy = NR HT/Tamoxifen = NR Localised stage = 68.9% Regional/distant stage = 30.3% ER+ = 72%	Self-administered questionnaire administered at variable times before diagnosis. Questionnaire assessed intensity, frequency, and duration Pre-diagnosis lifetime recreational PA (h/wk/y) during high school, between the ages of 18–24, 25–34, 35–44 and 45–54 y, and during the 3 y pre-enrollment (recent PA).
Abrahamson (2006) USA, Prospective cohort study	N = 1264 A-C death = 290 BC-R death = 247 Recurrence = NR, 1990–1992, Median follow-up = 8.3 (range = 0.25–9.8) y	Median age = 42 (range = 20–54) y Postmenopausal = 22% BMI ≥ 25 = 38% White = 75% Family history = NR	Chemotherapy = NR Hormone therapy (HT)/Tamoxifen = NR Local stage = 57% Regional/distant stage = 43% ER+ = 61.8% PR+ = 59%	Interview-administered questionnaire assessed pre-diagnosis PA assessed at age's 12–13 y, 20 y and the year before diagnosis. Questionnaire assessed frequency of vigorous activities (lap swimming, dance, basketball, gymnastics, running, fast cycling, aerobics, or field hockey) and moderate activities (brisk walking, volleyball, recreational tennis, softball, leisurely cycling, or golfing).
Enger (2004) USA, Prospective cohort follow-up of case-control study	N = 717 A-C death = 263 BC-R death = 251 Recurrence = NR 1983–1989, Median follow-up = 10.4 (range = 0.3–15.1) y	Aged 21–30 y = 10% Aged 31–40 y = 90% Premenopausal = 100% BMI < 20.4 = 24.4% BMI 20.4–24.8 = 50.2% BMI ≥ 24.9 = 25.4% Race = NR Family history = NR stage = 39(4)% HR-status = NR	Chemotherapy = NR HT/Tamoxifen = NR In situ stage = 10% Localized stage = 47% Regional(distant)	Interviewer-administered questionnaire administered 1 y after diagnosis. Questionnaire assessed pre-diagnosis recreational PA during lifetime (from first menses to 1-y prior to diagnosis) and during the year before diagnosis. For each activity the age started and stopped, the type and the average number of h/wk of participation was recorded.
Studies including more recent recreational pre-diagnosis physical activity analysis only:
Schmidt (2013) (MARIE), Germany, Prospective cohort follow-up of case-control study	N = 3393 A-C death = 367 BC-R death = 243 Recurrence = 330 2001–5 in Hamburg and 2002–5 in the Rhein-Neckar-Karlsruhe region. Median follow-up = 5.6 y	Mean age = 62.7 (IQR = 58–67) y Menopausal status = NR Mean BMI = 22.78 White = NR Family history = NR	Chemotherapy = 47.9% HT/Tamoxifen = 77.5% Stage data = NR ER+/PR+ = 58.0% ER-/PR- = 15.3%	Pre-diagnosis recreational PA since age 50 y until breast cancer diagnosis (median 12.7 y, range 7.6–16.7 y) was assessed using an interviewer-administered questionnaire. MET-h/wk were calculated by summing the average hours per week spent walking, cycling, engaged in sports or occupation and household PA.
Williams (2013) (NWRHS), USA, Prospective cohort study	N = 79,124 A-C death = NR BC-R = 111 Recurrence = NR 1999–2001, 1991–3 and 1998–2001, Mean follow-up = 11.0 ± 2.1 y	Mean age at death or December 31, 2008 = 54.7 y Postmenopausal = 43.2% Mean BMI = 23.9 Race = NR Family history = 8.9%	Chemotherapy = NR HT = NR Stage data = NR HR-status = NR	Self-administered questionnaires assessed distance run and walked as average miles run/walked per week at the time of enrolment and preceding 5 years (the most recent distance was used for analyses). Pace was determined by the question ‘‘During your usual run/walk, how many minutes does it take for you to run/walk one mile?’’ Run/walk data was then converted to MET-h/wk.
Emaus (2010) Norway, Prospective cohort study	N = 1364 A-C death = 429 BC-R death = 355 Recurrence = NR 1975–2005, Mean interval between diagnosis and end of follow-up = 8.2 ± 6.6y	Mean age = 57.5 ± 8.9y Postmenopausal = 61% Mean BMI = 24.0 ± 4.1 Race = NR Family history = NR	Chemotherapy = NR HT/Tamoxifen = NR Stage I = 48.8% Stage II = 41.3% Stage III = 4.6% Stage IV = 5.3% HR-status = NR	Self-administered questionnaire completed mean 11.5 y before diagnosis. Pre-diagnosis recreational PA 1 y preceding each survey. Assessed usual level of PA during leisure time in the previous year using 1 of 4 categories including sedentary activities, at least 4 h/wk engaging in PA, at least 4 h/wk exercising to keep fit and participating in recreational athletics, and regular, vigorous training, or competitive sports several times a week.
Hellmann (2010) (CHCS), Denmark, Prospective cohort study	N = 528 A-C death = 323 BC-R death = 178 Recurrence = NR Four points of follow-up: 1976–8, 1981–3, 1991–4, 2001–3, Median follow-up = 7.8 (range = 0.04–29.2) y	Median age = 67 (range = 33.1–95.4) y Postmenopausal = 84% BMI ≥ 25 = 49.6% Race = NR Family history = NR	Chemotherapy = 7.4% HT/Tamoxifen = 7.4% Local stage = 56.2% Regional = 33.7% Distant = 6.3% HR-status = NR	Self-administered questionnaire completed mean 6.7 y before diagnosis. Frequency of leisure time pre-diagnosis PA as categorised into inactive, moderate = 2–4 h/wk, high = > 4h/wk.
Borugian (2004) USA, Prospective cohort study	N = 603 A-C death = 146 BC-R death = 112 Recurrence = NR 1991–2, Median follow-up = 8.1 y	Mean age = 55 (± 11) y Postmenopausal = 61% Mean BMI = 26 (± 4.6) Caucasian = 88% Family history = 15.9%	Chemotherapy = 36% HT/Tamoxifen = 43% Stage = NR ER+ = 76.4%	Self-administered questionnaire given 2 mo after surgery assessed how often (per week, month or year) the participant does each of the following: physical exercise, active sports, jogging or running, swimming or taking long walks, and gardening or fishing or hunting, as well as blocks walked and flights of stairs climbed on average each day.
Rohan (1995) Australia, Prospective cohort follow-up of case-control study	N = 451 A-C death = 123 BC-R death = 112 Recurrence = NR 1982–4, Median follow-up = 5.5 (range = 0.5–7.1) y	Median age = 55.2 y Postmenopausal = 64% BMI ≥ 26 = 42% Race = NR Family history = 8.3%	Chemotherapy = NR HT/Tamoxifen = NR Stage = NR ER+ = 54.9% ER- = 28.4%	Interview-administered questionnaire completed at variable times after diagnosis. Pre-diagnosis PA in the year pre-diagnosis was assessed. Participants reported how many h/wk they spend doing light, moderate and vigorous recreational activities. H/wk were converted to kcal/min.
Studies that assessed both more recent pre-diagnosis and post-diagnosis recreational physical activity:
Irwin (2008) (HEAL), USA, Prospective cohort study	Pre-diagnosis: N = 933 A-C death = 164 BC-R death = 115 Post-diagnosis: N = 688 A-C death = 53 BC-R death = 30 Recurrence = 56 1995–8, Median follow-up = 6 (range = 5–8) y	Mean age = 55.5 (range = 35–64) y Postmenopausal = 60% Mean BMI = 26.7 Non-Hispanic white = 55.6% Family history = NR	Chemotherapy = 42% HT/Tamoxifen = 51% Local stage = 69% Regional stage = 31% ER+ = 67%	Interviewer-administered questionnaire administered at a median of 5 mo after diagnosis and again at a median of 2.5 y after diagnosis. Modifiable Activity Questionnaire (Kriska, 1997) included the assessment of recreational, occupational and household PA (type, duration and frequency converted to MET-h/wk) in the year preceding each interview.
Irwin (2011) (WHI), USA, Prospective cohort study	Pre-diagnosis: N = 4643 A-C death = 350 BC-R death = 194 Post-diagnosis: N = 2910 A-C death = 186 BC-R death = 86 1993–1998, Pre-diagnosis mean follow-up = 8 (± 1.3) y Post-diagnosis mean follow-up = 3.3 (± 1.8) y	Mean age at enrolment = 63.7 y Postmenopausal = 100% Mean BMI = 28. Non-Hispanic whites = 86% Family history = NR	Chemotherapy = NR HT/Tamoxifen = NR Local stage = 73% Regional stage = 27% ER+ = 76% ER- = 15%	Self-administered questionnaire administered at baseline (average 4.1 y before diagnosis) and years 3 and 6 post-enrolment. The questionnaire assessed frequency, duration, and intensity of walking outside the home and recreational PA in MET-h/wk conducted at the time of the assessment.
Studies including post-diagnosis recreational physical activity analysis only:
Bradshaw (LIBCSP) 2014, USA, Prospective cohort follow-up of case-control study	N = 1423 A-C death = 420 BC-R death = 195 Recurrence = NR 1996–7, Median survival time = 12.7 (range = 0.23–13.4) y	Mean age at diagnosis = 58.8 (± 12.7) y Postmenopausal = 68% BMI ≥ 25 = 53.8% Race = NR Family history = NR	Chemotherapy = 41.2% HT = 61.5% Stage = NR ER+ = 73.4% ER- = 26.6% PR+ = 64.1% PR- = 35.9%	Interview-administered questionnaire was carried out soon after diagnosis and again after approximately 5 y to assess recreational PA before and after diagnosis. The duration of participation (months per year) and average number of h/wk for each activity reported. PA levels were then converted to MET-h/wk.
Williams (2014) (NRWHS), USA, Prospective cohort follow-up of a prospective cohort study	N = 986 A-C death = NR BC-R death = 46 Recurrence = NR 1998–2001, Mean follow-up = 9.1 ± 0.8 y	Mean age = 53 y Postmenopausal = 81.3% Mean BMI = 24.0 Race = NR Family history = 19.9%	Chemotherapy = NR HT = NR Stage = NR HR-status = NR	Self-administered questionnaires were given a mean of 7.9 ± 7.3 y after diagnosis. The questionnaires assessed post-diagnosis running and walking using the same method as Williams 2013 above.
Bertram (2011) (WHEL), USA, Prospective cohort study	N = 2361 A-C death = 163 BC-R death = NR Recurrence = 295^b 1995–2000, Median follow-up = 7.1 (range = 1.0–10.8) y	Mean age = 53.9 y Postmenopausal = 80% Mean BMI = 27.1 BMI < 25.0 = 44.0% BMI ≥ 25–29.9 = 56.0% White = 86.6% Family history = NR	Chemotherapy = 68.2% HT/Tamoxifen = 68.3% Stage I = 40.6% Stage II = 45.2% Stage III = 14.3% HR-status = NR	Self-administered questionnaire administered after treatment at baseline and 1 y after. A 9-item PA measure adapted from the WHI study (see Irwin et al. 2011) assessed frequency, duration, and speed of walking outside the home and frequency and duration of participation in 3 intensities (mild, moderate, or vigorous) of exercise. Activity levels were converted into MET-h/wk.
Chen (2011) (SBCSS), China, Prospective cohort study	N = 4826 A-C death = 436 BC-R death = 450^c Recurrence = NR 2002–6 Median follow-up = 4.3 y	Mean age = 53.5 (± 10) y Postmenopausal = 51.1% Mean BMI = 24.1 (3.4) Race = 100% Chinese Family history = 5.6%	Chemotherapy = 92.2% HT/Tamoxifen = 51.9% Stage I = 34.8% Stage II = 51.1% Stage III = 9.4% ER+ = 50.3% ER- = 27.4%	Interviewer-administered questionnaire administered at 6, 18, 36 mo after diagnosis. Participants asked whether they exercised regularly (≥ 2 h/wk) or not. If the answer was “Yes”, they reported up to 5 of the most common activities. Frequency and duration was obtained for all exercise activities. PA was then converted to MET-h/wk.
Sternfield (2009) (LACE), USA, Prospective cohort study	N = 1970 A-C death = 187 BC-R death = 102 Recurrence = 225 1997–2000, Mean follow-up = 7.2 ± 1.5 y	Mean age = 61.5 y Postmenopausal = 67.2% Mean BMI = 27.5 White = 80% Family history = 20%	Chemotherapy = 69% HT/Tamoxifen = 76.2% Stage I = 47.8% Stage II = 49.2% Stage III = 3% ER+/PR+ = 64.6% ER-/PR- = 17.6% ER+/PR- = 15.2% ER-/PR+ = 2.7%	Self-administered questionnaire given at study entry (mean 1.9 y after diagnosis) assessed PA in preceding 6-mo. Frequency, intensity and duration of job/work-related PA, household chores, caregiving and home maintenance PA, recreational PA and transport (motorised & active) was assessed. NHS activity score also calculated (see Holmes et al., 2005).
First author (trial name), country, design	N Sample and outcomes, years diagnosed and follow-up duration	Sample characteristics	Treatment, disease stage and HR status data	PA assessment details
Holick (2008) (CWLS), USA, Prospective cohort follow-up of case-control studies	N = 4482 A-C death = 412 BC-R death = 109 Recurrence = NR 1998–2001, Mean follow-up = 5.5 ± 1.1 y	Mean age = 59 (range = 20–79) y Postmenopausal = 72.7% Mean BMI = 25.6 Caucasian = 98.7% Family history = 20.4%	Chemotherapy = NR HT/Tamoxifen = NR Local stage = 73% Regional stage = 27% HR-status = NR	Interviewer-administered questionnaire given 2 y after diagnosis assessed post-diagnosis and treatment PA in the year before enrolment. The questionnaire was modelled on NHS PA questionnaire (Holmes et al., 2005) and included calculation of the NHS activity score.
Holmes (2005) (NHS), USA, Prospective cohort study	N = 2987 A-C death = 463 BC-R = 280 Recurrence = 370 1984–98, Median follow-up = 8 y	Age range = 30–55 y Menopausal status = NR Mean BMI = 25.1 Non-Hispanic white = 98% Family history = 23%	Chemotherapy = 33.7% HT/Tamoxifen = 34.7% Stage I = 57.7% Stage II = 35.1% Stage III = 7.2% HR-status = NR	Post-diagnosis and post-treatment PA in the year before enrolment was assessed via a self-administered questionnaire administered a median 38 mo after diagnosis. The NHS activity score in the past year was calculated from the average time per week spent at each of the following 8 activities (frequency, intensity duration): walking or hiking, jogging or running, cycling, swimming laps, tennis, calisthenics, aerobics, squash or racquetball

BCFR, Breast Cancer Family Registry; CHCS, Copenhagen City Heart Study; CTS, California Teachers Study; CWLS, Collaborative Women's Longevity Study; HEAL, Health, Eating, Activity, and Lifestyle; LACE, Life After Cancer Epidemiology Study; LIBCSP, Long Island Breast Cancer Study Project; MARIE, Mammary carcinoma Risk factor Investigation; NHS, Nurses’ Health Study; NWRHS, National Walkers’ and Runners’ Health Studies; PACE, Prospective Analysis of Case-Control Studies on Environmental Factors and Health; SBCSS, Shanghai Breast Cancer Survival Study; WHEL, Women's Healthy Eating and Living Study; WHI, Women’s Health Initiative.

ER, oestrogen receptor; HR, hormone receptor; HT, hormone treatment; NR, not reported, PR, progesterone receptor.

^a Breast cancer recurrence and breast cancer progression and new breast cancer primaries combined; ^b Breast cancer recurrence and new breast cancer primaries combined; ^c Breast cancer-related deaths and recurrence combined.

Figure 2. Risk of bias across each item of the Newscastle-Ottawa Scale.

Table II. Risk of bias summary: review authors’ judgments about each risk of bias item for each included study using the Newcastle-Ottawa Scale.

	Representativeness of the exposed cohort	Selection of the non-exposed cohort	Ascertainment of exposure (i.e. physical activity levels)	Demonstration that breast cancer was not present at start of study	Comparability of cohorts on the basis of the design or analysis, A*	Comparability of cohorts on the basis of the design or analysis, B*	Assessment of outcome	Was follow up long enough for outcomes to occur	Adequacy of follow up of cohorts	Star Total
Rohan, 1995	1	1	1	0	0	1	1	1	1	7
Borugian, 2004	1	1	0	0	1	1	1	1	0	6
Enger, 2004	0	1	1	0	0	1	1	1	0	5
Holmes, 2005	0	1	0	0	1	1	1	1	1	6
Abrahamson, 2006	1	1	1	0	0	1	1	1	1	7
Dal Maso, 2008	1	1	1	0	0	1	1	1	1	7
Holick, 2008	1	1	0	0	1	0	1	1	0	5
Irwin, 2008	1	1	1	0	1	1	1	0	0	6
Friedenreich, 2009	1	1	1	0	1	1	1	1	0	7
Sternfield, 2009	1	1	0	0	1	1	1	1	1	7
West-Wright, 2009	0	1	0	1	0	1	1	1	1	6
Emaus, 2010	1	1	0	1	0	1	1	1	1	7
Hellmann, 2010	1	1	0	1	1	1	1	1	1	8
Keegan, 2010	1	1	0	0	0	1	1	1	1	5
Bertram, 2011	1	1	0	0	0	1	1	1	1	6
Chen, 2011	1	1	1	0	1	1	1	0	0	6
Irwin, 2011	1	1	0	1	0	1	1	1	1	7
Cleveland, 2012	1	1	1	0	0	1	1	1	0	6
Schmidt, 2013	1	1	1	0	1	1	1	1	1	8
Williams, 2013	0	1	0	1	0	1	1	1	0	5
Bradshaw, 2014	1	1	1	0	0	1	1	1	0	6
Williams, 2014	0	1	0	0	0	1	1	1	0	4

Figure 3. Funnel plot of lifetime pre-diagnosis recreational physical activity and all-cause death. The effect estimate line is shown as a dashed line.

Figure 4. Forest plot with random effects overall hazard ratio for association between lifetime recreational (pre-diagnosis) physical activity (highest vs. lowest physical activity categories) and all-cause death in breast cancer survivors. Red squares indicate hazard ratios (HRs), and solid horizontal lines represent 95% confidence intervals (CIs). The vertical solid line indicates point of no effect. Black diamond indicates overall effect.

Figure 5. Forest plot with random effects overall hazard ratio for association between lifetime recreational (pre-diagnosis) physical activity (highest vs. lowest physical activity categories) and breast cancer-related death in breast cancer survivors.

Figure 6. Forest plot with random effects overall hazard ratio for association between recent pre-diagnosis recreational physical activity (highest vs. lowest physical activity categories) and all-cause death in breast cancer survivors.

Figure 7. Forest plot with random effects overall hazard ratio for association between recent pre-diagnosis recreational physical activity (highest vs. lowest physical activity categories) and breast cancer-related death in breat cancer survivors.

Figure 8. Forest plot with random effects overall hazard ratio for association between post-diagnosis recreational physical activity (highest vs. lowest physical activity categories) and all-cause death in breast cancer survivors.

Figure 9. Forest plot with random effects overall hazard ratio for association between post-diagnosis recreational physical activity (highest vs. lowest physical activity categories) and breast cancer-related death in breast cancer survivors.

Figure 10. Forest plot with random effects overall hazard ratio for association between post-diagnosis meeting recommended physical activity guidelines (meeting vs. not meeting physical activity guidelines) and all-cause death in breast cancer survivors.

Figure 11. Forest plot with random effects overall hazard ratio for association between post-diagnosis meeting recommended physical activity guidelines (meeting vs. not meeting physical activity guidelines) and breast cancer-related death in breast cancer survivors.

Figure 12. Forest plot with random effects overall hazard ratio for association between Pre-diagnosis physical activity (highest vs. lowest physical activity categories) and breast cancer events in breat cancer survivors.

Figure 13. plot with random effects overall hazard ratio for association between Post-diagnosis physical activity (highest vs. lowest physical activity categories) and breast cancer events in breast cancer survivors.

Table III. Summary of random effects overall hazard ratios (HR) and 95% confidence intervals (CI) for association between recreational physical activity (PA) variables and death and breast cancer (BC) events in breast cancer survivors.

PA variable	Outcome	Effect estimate HR (95% CI)	I^2
Lifetime pre-diagnosis PA	All-cause death	0.82 (0.70–0.96)*	49%
	BC-related death	0.73 (0.54–0.98)*	67%
More recent pre-diagnosis PA	All-cause death	0.73 (0.65–0.82)**	0%
	BC-related death	0.84 (0.73–0.97)*	0%
Pre-diagnosis PA	BC events	0.72 (0.56–0.91)**	0%
Post-diagnosis PA	All-cause death	0.52 (0.43–0.64)**	54%
	BC-related death	0.59 (0.45–0.78)*	57%
	BC events	0.79 (0.63–0.98)*	0%
Post-diagnosis meeting recommended PA guidelines	All-cause death BC-related death	0.54 (0.38–0.76)** 0.67 (0.50–0.90)**	87% 73%

*p < 0.05; **p < 0.01.

Table IV. Summary of BMI and menopausal subgroup analyses by recreational physical activity (PA) variable.

PA variable	Subgroups	Outcome	Studies (N)	Effect estimate HR (95% CI)	I^2
Lifetime pre-diagnosis PA	BMI < 25 kg∙m^2	All-cause death	3	0.63 (0.45–0.90)**	34%
		BC-related death	2	0.89 (0.53–1.52)	9%
	BMI ≥ 25 kg∙m^2	All-cause death	3	0.75 (0.56–1.00)*	6%
		BC-related death	2	0.49 (0.32–0.74)**	0%
More recent pre-diagnosis PA	BMI < 25 kg∙m^2	All-cause death	3	1.07 (0.65–1.77)	84%
		BC-related death	0
	BMI ≥ 25 kg∙m^2	All-cause death	3	0.83 (0.57–1.23)	48%
		BC-related death	0
Post-diagnosis PA	BMI < 25 kg∙m^2	All-cause death	5	0.44 (0.30–0.64)**	51%
		BC-related death	3	0.47 (0.20–1.10)	76%
	BMI ≥ 25 kg∙m^2	All-cause death	3	0.50 (0.32–0.78)**	49%
		BC-related death	3	0.51 (0.35–0.74)**	10%
Lifetime pre-diagnosis PA	Premenopause	All-cause death	2	1.37 (0.68–2.79)	65%
		BC-related death	2	1.18 (0.71–1.97)	8%
	Postmenopause	All-cause death	2	0.46 (0.26–0.83)**	50%
		BC-related death	2	0.58 (0.36–0.94)*	0%
More recent pre-diagnosis PA	Premenopause	All-cause death	0
		BC-related death	2	1.39 (0.72–2.68)	0%
	Postmenopause	All-cause death	0
		BC-related death	2	0.77 (0.45–1.32)	0%
Post-diagnosis PA	Premenopause	All-cause death	2	0.44 (0.10–2.01)	82%
		BC-related death	2	0.55 (0.37–0.82)**	0%
	Postmenopause	All-cause death	2	0.44 (0.24–0.80)**	60%
		BC-related death	2	0.75 (0.58–0.98)*	0%

BC, breast cancer. * p < 0.05; ** p < 0.01.

Table V. Summary of HR-status and stage subgroup analyses by recreational physical activity (PA) variable.

PA variable	Subgroups	Outcome	Studies (N)	Effect estimate HR (95% CI)	I^2
More recent pre-diagnosis PA	ER-	All-cause death	2	0.93 (0.63–1.38)	0%
		BC-related death	0
	ER+	All-cause death	2	0.77 (0.59–1.02)	29%
		BC-related death	0
Post-diagnosis PA	ER-	All-cause death	2	0.83 (0.39–1.75)	0%
		BC-related death	0
	ER+	All-cause death	2	0.34 (0.14–0.83)*	75%
		BC-related death	0
	ER-/PR-	All-cause death	3	0.56 (0.41–0.77)**	0%
		BC-related death	2	0.58 (0.25–1.36)	65%
	ER+/PR+	All-cause death	3	0.58 (0.22–1.54)	90%
		BC-related death	2	0.32 (0.12–0.86)	82%
More recent pre-diagnosis PA	Local disease	All-cause death	2	0.71 (0.53–0.95)*	0%
		BC-related death	0
	Regional disease	All-cause death	2	0.83 (0.58–1.20)	0%
		BC-related death	0
Post-diagnosis PA	Stage I	All-cause death	2	0.31 (0.10–0.95)*	64%
		BC-related death	0
	Stage II-III	All-cause death	2	0.57 (0.41–0.79)**	0%
		BC-related death	0

BC, breast cancer; ER, oestrogen receptor, PR, progesterone receptor. * p < 0.05; ** p < 0.01.