Breast cancer—epidemiology, risk factors, and genetics
BMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7261.624 (Published 09 September 2000) Cite this as: BMJ 2000;321:624
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Dear Sir
I feel I must comment on the statement made about Body Mass Index
(BMI) in the table on established or probable risk factors for breast
cancer in the paper Breast cancer – epidemiology, risk factors, and
genetics by McPherson K, Steel CM and Dixon JM (BMJ 2000; 321: 624-628)
(1). Apart from the obvious mis-statement that the high-risk group for
premenopausal women are those with a BMI > 35 I have grave doubts about
the usefulness of an arbitrary dividing value of 35 for BMI in the
discussion of risk factors for breast cancer.
It seems clear that the implication of the statements made here is
that for post menopausal women there are two groups: a low risk group with
BMI of 35 or under, and a high risk group with BMI of over 35, and the
relative risk comparing the two groups is 2.
It is also implied that for premenopausal women the situation is
reversed: there is a low risk group with BMI over 35 and a high-risk group
with BMI of 35 or under, and the relative risk is 0.7.
A few moments thought suggests that a BMI of 35 or more indicates a
high level of obesity. The results of NHANES, (Kuczmarski RJ, 1997) (2)
in the USA suggests that BMI above 25 indicates overweight and over 30
indicates obesity. In a pooled analysis of cohort studies on breast
cancer risk by van den Brandt et al (2000) (3), the proportion of
premenopausal cases with BMI values above 35 was not given but the
proportion of cases with BMI above 33 was 20/703 = 2.84%. This would
imply that at least 100 – 2.84 = 97.16% of cases are part of the high-risk
group.
The paper (3) also indicates that for post-menopausal women the
proportion of cases with BMI over 33 is 185/3206 = 5.97%, so the
proportion in the high-risk group here with BMI > 35 must apparently be
smaller than this.
This seems to indicate that dividing women into two high/low risk
groups according to BMI above or below 35 is not helpful.
What the paper (3) does point out is that in premenopausal women the
relative risk for those with a BMI above 31 is 0.54 (95% CI : 0.34, 0.85),
compared to premenopausal women with a BMI of less than 21. For post-
menopausal women, compared with those with a BMI of less than 21 that the
relative risk for those whose BMI was greater than 28 was 1.26 (95% CI :
1.09, 1.46) and that it did not increase further for BMI values greater
than 28.
When relative risks are given the groups being compared should always
be clearly defined.
Yours faithfully
Alan C C Gibbs
Lecturer in Medical Statistics
REFERENCES
1. McPherson K, Steel CM, Dixon JM. Breast cancer – epidemiology
risk factors and genetics. BMJ 2000; 321: 624-8.
2. Kuczmarski RJ, Carroll MD, Flegal KM, Troiano RP. Varying body
mass index cut-off points to describe overweight prevalence among US
adults NHANES III (1998 to 1994). Obes Res 1997; 5: 542-8.
3. van den Brandt PA et al. Pooled analysis of prospective cohort
studies on height, weight and breast cancer risk. Am J Epidemiol 2000;
152: 514-27.
Competing interests:
None declared
Competing interests: No competing interests
Dear Sir
With reference to the paper on breast cancer (1) I should like to
make the following points:
Age standardised incidence and mortality from breast cancer are not
the highest in the world in the United Kingdom. Recent information
suggests that mortality rates are higher in Ireland, Denmark, Finland,
Malta and the Netherlands, and that incidence rates are higher in Denmark,
Sweden, Ireland, Finland, the Netherlands, Switzerland, France, Belgium
and Luxembourg, considering European countries only (2). In addition,
data from Cancer incidence in five continents (3) (volume 7) shows that in
the most recent period covered (1988-92) standardised incidence rates were
higher in the U.S.A. (whites and blacks), Israel (all jews), Canada and
New Zealand.
One of the tables claims to show standardised mortality for breast
cancer in different countries, but in fact gives standardised incidence
based on data published in Cancer incidence in five continents (volume 6)
relating to the period 1983-87 and published in 1992 (4). More up to date
figures for 1988-92 were available in 19973.
It should also be noted that for premenopausal women the high-risk
group were those whose body mass index was less than 35 (5).
Yours faithfully
Alan C C Gibbs
References
1. McPherson K, Steel CM, Dixon JM. Breast cancer – epidemiology,
risk factors, and genetics. BMJ 2000; 321: 624-8.
2. Bray F, Sankila R, Ferlay J, Parkin DM. Estimates of cancer
incidence and mortality in Europe in 1995. Eur J Cancer 2002; 98: 99-166.
3. Parkin DM, Muir CS, Whelan SL, Gao Y-T, Ferlay J, Powell J (eds),
Cancer incidence in five continents, vol VI, Lyon, IARC, 1992.
4. Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J (eds), Cancer
incidence in five continents, vol VII, Lyon, IARC, 1997.
5. Friedenreich CM. Review of anthropometric factors and breast
cancer risk. European J Cancer Prevention 2001; 10: 15-32.
Competing interests: No competing interests
Dear Sir:
This particular risk factor is seldom mentioned, but has been
published for some time now.
International Journal of Epidemiology, Vol 18, 300-304
Early abortion and breast cancer risk among women under age 40
HL Howe, RT Senie, H Bzduch and P Herzfeld
Division of Epidemiology, New York State Department of Health.
Odds ratios (OR) were significantly elevated among those with an
induced abortion (OR = 1.9) and a spontaneous abortion (OR = 1.5).
Competing interests: No competing interests
Please correct an inaccuracy in your Web-based article. Under
Hormonal Control, you referenced the NSABP Breast Cancer Prevention Trial
(BCPT) and have included an inaccurate sample size. The BCPT included
13,388 pre- and postmenopausal women, not 3,338.
If you have made this error in the hardcopy of your manuscript,
please make this correction prior to publication.
Thank you for your attention to this matter.
Competing interests: No competing interests
The review by McPherson, Steel and Dixon (1) states "Smoking is of no
importance in the aetiology of breast cancer." The authors appear unaware
of the mounting evidence in support of a tobacco smoke-breast cancer
relationship.
Seven of the eight published studies examining passive smoking and
breast cancer suggest an increased risk of breast cancer associated with
long term passive smoke exposure among women who have never smoked,
particularly premenopausal breast cancer.(2,3,4) Furthermore, when
passive smoke exposure is controlled for in these studies, active smoking
also appears to be a risk factor for breast cancer.(2,3) Both long term
passive smoking among never-smoking women and active smoking may almost
double breast cancer risk.(2,3) Polycyclic aromatic hydrocarbons (PAH)
are found in tobacco smoke, cause mammary cancer experimentally and may
contribute to the development of human breast cancer.(5)
Given the high prevalence of regular passive smoke exposure and of
active smoking among women in most industrialized nations, smoking may, in
fact, turn out to be of considerable importance in the aetiology of breast
cancer.
1. McPherson K, Steel CM, Dixon JM. Breast cancer- epidemiology,
risk factors, and genetics. Clinical Review, BMJ 321(624-628)
2. Wells AJ. Re: "Breast cancer, cigarette smoking, and passive
smoking". Am J Epidemiol. 1998 May 15;147(10):991-2.
3. Johnson KC, Hu J, Mao Y and The Canadian Cancer Registries
Epidemiology Research Group. Passive and Active Smoking and Breast
Cancer Risk in Canada 1994-97. Cancer Causes and Control. 11: 211-221.
2000.
4. Jee SH, Ohrr H, Kim IS, Effects of husbands' smoking on the
incidence of lung cancer in Korean women. Int J Epidemiol. 1999
Oct;28(5):824-8.
5. Rundle A, Tang D, Hibshoosh H, Estabrook A, Schnabel F, Cao W,
Grumet S, Perera FP. The relationship between genetic damage from
polycyclic aromatic hydrocarbons in breast tissue and breast cancer.
Carcinogenesis 2000 Jul;21(7):1281-9
Competing interests: No competing interests
Sir,
The protective effect of breast feeding against premenopausal forms
of breast cancer has been mentioned by some ( Mac Mahon- no ref available
; Mc tiernan, A et al . American Journal of Epidemiology. " Evidence for a
protective effect of lactation on risk of breast cancer in young women")
and denied by others (American Journal of Epidemiology. 1986 Vol 124; 331-
347; "Unilateral breast feeding and breast cancer" Ing, R. Lancet 1977;
Vol 2. 124-127). However this effect has not been found by others.
This issue might be difficult to settle due to different definitions
of breast feeding practices and ways of measuring duration and intensity
of breast feeding.
I would love the author´s comments on this.
Thank you.
Competing interests: No competing interests
TO THE EDITOR:
McPherson et al note that the breast tissue of the young is
particularly sensitive to radiation carcinogenesis. (1) Their diagram
demonstrates the increased cumulative lifetime risk of breast cancer in
women who were A-bomb survivors as teenagers. (1) More commonly seen in
practice than A-bomb survivors, are women treated for Hodgkin’s disease as
children or adolescents. One series examining this group demonstrated a
cumulative probability of breast cancer by 40 years of age of 35%. (2)
Fortunately the risk of radiation induced cancers falls sharply with the
age at exposure - the risk from radiation scattered to the contralateral
breast when treating breast cancer or DCIS is small indeed. (3) Similarly
this explains why the benefits of mammography outweigh radiation
carcinogenesis in the appropriate age groups.
Sean Bydder, Registrar.
s_bydder@hotmail.com
Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands
Western Australia Australia WA 6008
(1) McPherson K, Steel, CM. Dixon JM. Breast cancer – epidemiology,
risk factors and genetics. BMJ 2000; 321:624-628.
(2) Joseph DJ, Spry N, Bydder S. Adjuvant radiotherapy for DCIS.
Lancet. 2000;355:2072.
(3) Bhatia S, Robison LL, Oberlin O, Greenberg M, Bunin G, Fossati-
Bellani F, Meadows AT Breast cancer and other second neoplasms after
childhood Hodgkin's disease.
N Engl J Med 1996;334:745-51.
Competing interests: No competing interests
The recent paper on breast cancer [1] has overlooked an important
risk reduction factor - vitamin D, either through production in the skin
through the action of solar ultraviolet B (UV-B) radiation on cholesterol
or through dietary supplements. Using the U.S. Atlas of Cancer Mortality
[2] and ground-based or space-based UV-B exposure data, it can be shown
that 15-20% of the breast cancer mortality in the U.S. from 1970-1994
could have been prevented through adequate amounts of UV-B/vitamin D [3].
The diet in the different quadrants of the U.S. is similar enough that
diet has a similar effect for those living in the U.S., so cannot explain
the geographic difference in the U.S. Indeed, information on UV-B and
vitamin D as risk reduction factors for breast cancer has been in the
literature for the past decade, but has not received the attention it
deserves. Not only breast cancer, but also mortality from about a dozen
other cancers could be reduced by adequate amounts of vitamin D as well
[3]. The interested reader is urged to look at some of the papers in the
bibliography that follows.
[1] McPherson K, Steel, CM, Dixon JM. Breast cancer epidemiology,
risk factors, and genetics, BMJ 2000;321:624-628.
[2] Devesa, SS, Grauman, DJ, Blot, WJ, Pennello, GA, Hoover, RN,
Fraumeni, JF Jr, Atlas of Cancer Mortality in the United States, 1950-
1994. NIH Publication No. 99-4564, 1999.
http://www.nci.nih.gov/atlas/mortality.html
[3] Grant WB, Slusser JR, An estimation of excess cancer mortality in
the United States due to inadequate ultraviolet-B radiation and vitamin D,
in preparation.
Bibliography of papers relating to cancer and vitamin D:
PubMed - source of abstracts for references listed below (search by
author's last name, initials and year of publication)
http://www.ncbi.nlm.nih.gov/pubmed/
Ahonen, MH, Zhuang, YH, Aine, R, Ylikomi, T, Tuohimaa, P. Androgen
receptor and vitamin D receptor in human ovarian cancer: growth
stimulation and inhibition by ligands. Int J Cancer 2000;86:40-6.
Blutt, S, Weigel, N. Vitamin D and prostate cancer. Proc Soc Exp
Biol Med 1999;221:89-98.
Colston, KW, Perks, CM, Xie, SP, Holly, JMP. Growth inhibition of
both MCF-7 and Hs578T human breast cancer cell lines by vitamin D
analogues is associated with increased expression of insulin-like growth
factor binding protein-3. J Molec Endocrinol 1998;20:157-62.
Feldman, D, Zhao, XY, Krishnan, AV. Editorial/mini-review: Vitamin D
and prostate cancer. Endocrinology 2000;141:5-9.
Garland, FC, Garland, CF, Gorham, ED, Young, JF. Geographic
variation in breast cancer mortality in the United States: A hypothesis
involving exposure to solar radiation. Prev Med 1990;19:614-22.
Garland, FC, Garland, CF, Gorham, ED. Calcium and vitamin D. Their
potential roles in colon and breast cancer prevention. Ann NY Acad Sci
1999;889:107-19.
Gorham, ED, Garland, CF, Garland, FC. Acid haze air pollution and
breast and colon cancer mortality in 20 Canadian cities. Can J Publ
Health 1989;80:96-100.
Gorham, ED, Garland, FC, Garland, CF. Sunlight and breast cancer
incidence in the USSR. Int J Epidemiol 1990;19:820-4.
Hiatt RA, Krieger N, Lobaugh B, Drezner MK, Vogelman JH, Orentreich
N. Prediagnostic serum vitamin D and breast cancer. J Natl Cancer Inst
1998;90:461-3.
Janowsky, EC, Lester, GE, Weinberg, CR, Millikan, RC, Schildkraut,
JM, Garrett, PA, Hulka, BS. Association between low levels of 1,25-
dihydroxyvitamin D and breast cancer risk. Public Health Nutr 1999;2:283-
91.
John, EM, Schwartz, GG, Dreon, DM, Koo, J. Vitamin D and breast
cancer risk: the NHANES I epidemiologic follow-up study, 1971-1975 to
1992. National Health and Nutrition Examination Survey. Cancer Epidemiol
Biomarkers Prev 1999;8:399-406.
Koli, K, Keski-Oja, J. 1alpha,25-dihydroxyvitamin D3 enhances the
expression of transforming growth factor beta1 and its latent form binding
protein in cultured breast carcinoma cells, Cancer Res 1995;55:1540-6.
Koli, K, Keski-Oja, J. 1alpha,25-dihydroxyvitamin D3 and its
analogues down-regulate cell invasion-associated proteases in cultured
malignant cells. Cell Growth Differ 2000;11:221-9.
Lefkowitz, ES, Garland, CF. Sunlight, vitamin D, and ovarian cancer
mortality rates in U.S. women. Int J Epidemiol 1994;23:1133-6.
Lipkin, M, Newmark, HL. Vitamin D, calcium and prevention of breast
cancer: a review. J Am Coll Nutr 1999;18(5 suppl):392S-7S.
Newmark, HL. Vitamin D adequacy: a possible relationship to breast
cancer. Adv Exp Med Biol 1994;364:109-14.
Schwartz GG. Multiple sclerosis and prostate cancer: what do their
similar geographies suggest? Neurodepidemiology 1992;11:244-54.
Schwartz, GG, Hulka, BS. Is vitamin D deficiency a risk factor for
prostate cancer? (hypothesis). Anticancer Res 1990;10:1307-12.
Wang, Q, Yang, W, Uytingco, MS, Christakos, S, Wieder, R. 1,25-
Dihydroxyvitamin D3 and all-trans-retinoic acid sensitize breast cancer
cells to chemotherapy-induced cell death. Cancer Res 2000;60:2040-8.
Xier, SP, James, SY, Colston, KW. Vitamin D derivatives inhibit the
mitogenic effects of IGF-I on MCF-7 human breast cancer cells. J
Endocrinol 1997;154:495-504.
Xie, SP, Pirianov, G, Colston, KW. Vitamin D analogues suppress IGF-
I signalling and promote apoptosis in breast cancer cells. Eur J Cancer
1999;35:1717-23.
Competing interests: No competing interests
Typo in response "breast cancer risk and BMI"
In reference 2 the first date give for NHANES III should have been
1988 not 1998.
Competing interests:
None declared
Competing interests: No competing interests