Study: Women who exercise have lower breast cancer risk whether or not they have a family history of breast cancer

IN-DEPTH REVIEW OF RESEARCH

Study background:

Multiple studies have shown that physical exercise reduces breast cancer risk by approximately 20% among women in the general population. Prior studies did not look at family history of breast cancer. Whether exercise would reduce the risk of breast cancer for women with a family history of breast cancer is unclear.

A few studies have looked at exercise in women with BRCA1 and BRCA2 mutations—most were small, retrospective studies that grouped women with BRCA1 and BRCA2 mutations. The large prospective Sisters Study reported a 23% reduction in breast cancer risk for women who exercised 7 or more hours per week compared to those who exercised less than 1 hour per week. Among the participants, who were mostly postmenopausal, no association with family history was made.

Do these results hold up for women who are premenopausal and who have a family history of cancer?

Researchers of this study wanted to know:

Whether physical activity is linked to lower breast cancer risk in women with a family history of breast cancer.

Populations looked at in this study:

The participants in this study were from the Prospective Family Study Cohort (ProF-SC), an international group of women from the U.S., Canada, Australia and New Zealand, many of whom had a strong family history of breast cancer. This cohort was a combination of participants from six different study groups, as well as the Breast Cancer Family Registry (BCFR) and the Katherine Cuningham Foundation Consortium for Research (kConFab).

Participating women were enrolled before June 30, 2011 and had at least 2 months of follow-up, were 18 to 79 years old, had not had cancer or a bilateral mastectomy at the time of enrollment, and had sufficient family history reported to calculate familial risk scores.

Participants included 15,550 women from 6,530 families; 1,185 of the participants were women with known mutations: 659 had a BRCA1 mutation and 526 had a BRCA2 mutation. The average age of participants at enrollment was 46 years, and 59% of the women were premenopausal.

Study design:

At enrollment, each woman was asked about her demographic information, education, height, weight, menstrual and reproductive history, lifestyle factors including exercise, and personal and family history of cancer. Participants self-reported recreational physical activity by questionnaire. They were asked about moderate (e.g., brisk walking) and strenuous (e.g., running) exercise per week the prior 3 years and during their adolescence.

Exercise physiologists use metabolic equivalents to estimate how many calories are burned during physical activity. To quantify different types and amounts of physical activity, activity was counted as total metabolic equivalents (METs) per week: 1 hour of moderate exercise counted for 4 METs, while 1 hour of strenuous exercise counted for 7 METs. Participants were grouped into 5 groups or quintiles depending on the amount of regular exercise they reported:

• Quintile 1: those who exercised the least (the lowest 20)
• Quintile 2: those who exercised 21 to 40% of the maximum exercise group
• Quintile 3: those who exercised 41 to 60% of the maximum exercise group
• Quintile 4: those who exercise 61 to 80% of the maximum exercise group
• Quintile 5: those who exercised the most: 81 to 100% of the maximum amount

The amount of exercise that distinguished the lowest exercising group or least active women from the women with more activity was 10.75 MET (2.7 hours per week of moderate exercise or 1.5 hours per week of strenuous exercise).

Participants were asked about breast cancer for up to 20 years after enrollment. Self-reported breast cancer was confirmed by pathology reports for 81% of participants. The time in person-years was calculated from enrollment until breast cancer diagnosis, risk-reducing mastectomy, 80 years of age, departure from the study or death.

Factors that could potentially confuse results (confounding factors) were evaluated statistically. These factors included birth year, race, education level, having children, breast-feeding, cigarette smoking, alcohol intake, use of hormonal birth control, postmenopausal use of hormone replacement therapy, body mass (BMI), family history and mutation status.

Researchers were concerned that they might underestimate the effect of exercise during adolescence on BRCA1 or BRCA2 carriers because they are often diagnosed at a younger age, and women who were not diagnosed at enrollment may have been less susceptible. A group of 7,905 women who were diagnosed 5 years prior to the study were evaluated for their exercise levels compared to the main group of participants for analysis of adolescent exercise on breast cancer risk. This additional group of women included with 368 BRCA1 carriers and 336 BRCA2 carriers.

Study findings:  

• 896 (5.7%) of the 15,550 women participating in this study were diagnosed with breast cancer during the 160,000 person years of follow-up (an average of 10.3 years per woman):
  • 110 (12%) had a BRCA1 mutation
  • 69 (8%) had a BRCA2 mutation
  • 324 (36%) were diagnosed before age 50
• At the time of enrollment, the majority of women (86%) reported regular physical activity in the 3 prior years.
  • Average activity level was 24 METS (equivalent to 6 hours of moderate or 3.5 hours of strenuous activity per week).
• The majority of women (89%) reported some level of physical activity regularly during adolescence.
  • Average activity level was 43 METS (equivalent to 11 hours of moderate or 7 hours of strenuous activity per week).
• At the time of enrollment, the women who exercised different amounts did not differ in other ways except that exercise was associated with BMI and current smoking status. That is, a similar percentage of women were found in each exercise group at the time of enrollment in terms of birth year, race, education level, having children, breast-feeding, alcohol intake, use of hormonal birth control, postmenopausal use of hormone replacement therapy, family history and mutation status.
• Compared to breast cancer risk in women who exercised the least, participants who exercised more had 20% lower risk.
  • Women who got at least 10.75 metabolic equivalents of exercise per week (2.7 hours per week of moderate exercise such as walking or 1.5 hours per week of strenuous exercise such as running, had lower breast cancer risk than women who exercised less than that amount.
  • Women who exercised the least (less than 2.7 hours per week of moderate activity or 1.5 hours per week of strenuous exercise) had higher breast cancer risk than all other participants who exercised more.
  • Both moderate and strenuous exercise were associated with reduced breast cancer risk, as long as moderate exercise was more than 2.7 hours per week or strenuous was more than 1.5 hours per week.
  • Increasing the amount of exercise above the minimum level of activity was not correlated with a greater reduction of breast cancer risk.
• Recreational exercise reduced the risk of breast cancer in both women with and without a family history of breast cancer.
• No association was seen between adolescent physical activity and breast cancer risk for women in general. For women without a mutation, however, there was a reduced risk of breast cancer if they were active as adolescents. However, for women with BRCA mutations no reduction in risk was associated with adolescent activity.
  • In women with or without a mutation, physical activity as an adult at the time of enrollment was correlated with reduced risk, regardless of whether they had been active or inactive as adolescents.
  • In women with or without a mutation, physical inactivity as an adult at the time of enrollment was correlated with increased risk, regardless of whether they had been active or inactive as an adolescent.
  • When mutation status was considered:
    • For women with mutations in BRCA1 or BRCA2 (considered separately), physical activity as an adult at the time of enrollment was correlated with reduced risk, regardless of whether the woman was active or inactive as an adolescent.
    • For women without a mutation, there was a 14% reduced risk of breast cancer if that woman was active as an adolescent. When an expanded group that included women diagnosed within 5 years prior to enrollment was studied, adolescent physical activity was associated with a 9% reduced risk of breast cancer in women without a mutation.

Limitations:

One strength of this study is the large number of participants. It is the first study to look at the impact of physical activity separately in women with BRCA1 or BRCA2 mutations and to separately address moderate and strenuous activity levels.

One limitation of this study is that physical activity was self-reported and could be inaccurate.  Some responses required recollection of past events (for example, exercise frequency during participants’ teen years) that may not have been accurately remembered. However, the same amount of inaccuracy is expected among all participants and is not expected to differ among women who later report breast cancer compared to those who do not.

Another limitation is that the level of physical activity was only determined at the time of enrollment. Any changes in the amount of physical activity/exercise that occurred after enrollment but before breast cancer diagnosis (or other endpoint of participation) did not factor into the analysis.

Conclusions:

Exercise has many benefits, including improved cardiovascular health. Recreational physical activity lowers breast cancer risk regardless of a woman’s family history of breast cancer. Even if you were inactive as an adolescent, regular modest exercise as an adult may be beneficial in reducing your breast cancer risk.

Because women with a family history of breast cancer have a much higher baseline of absolute risk, a reduction of 20% in risk will be particularly impactful for them compared to women without a family history of breast cancer. Exercise may be a particularly effective way to reduce risk for women with the highest risk. The study authors point out that, "In terms of absolute numbers of breast cancer cases prevented, physical activity interventions could have a greater absolute effect if targeted to women at higher familial/genetic risk."

Clinical trials testing exercise interventions in adult mutation carriers would help to clarify whether exercise activity that was correlated with fewer breast cancer cases is directly responsible for the observed reduction in breast cancer risk.                                                                                       

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