 Carcinoma In Situ

Breast carcinoma in situ (CIS) occurs when cells have the appearance of invasive cancer
but do not invade adjacent tissue (ie they are non-invasive). Classic DCIS, confers a
risk of 1–2% per year to develop into invasive disease.1 Meanwhile, the risk of invasive
breast cancers was significantly increased in women with HR- first LCIS compared to
those with HR+ LCIS with hazard ratio 0.356 at 95% CI.2
 Benign Breast Disease
Benign breast disease (BBD) or “fibrocystic disease” are general terms applied to a
range of changes in breast tissue. These changes can be difficult to distinguish clinically
from invasive cancer until a biopsy is conducted for definitive diagnosis. Estimates of
occurrence differ according to the classifications used. Nevertheless, BBD is a fairly
common diagnosis. Many forms of BBD have no clinical symptoms, so the extent of
mammographic screening in the population also influences the frequency of diagnosis.
The relative risk associated with atypia benign breast disease was 4.24 at 95% CI, as
compared with a relative risk of 1.88 at 95% CI for benign breast disease with
proliferative changes without atypia and of 1.27 at 95% CI for nonproliferative lesions.3
Other research involving patient from Africa show similar result where women whose
biopsies showed proliferative disease with atypia were more than three-fold more likely
to develop breast cancer as compared with women who had nonproliferative disease
relative risk (RR) 3.29 at 95% CI.4
 Mammographic Breast Density
A measure of mammographic breast density is the percentage of dense (ie epithelial or
connective) tissue in the breast. Several classification systems of mammographic breast
density distinguish breast tissue comprised mainly of fat, degrees of density referring
to increasing ductal prominence and a pattern that is comprised mostly of dense tissue
(previously called “dysplasia”). The odds ratio for risk of breast cancer in those with
more than 75% density was 17.81 at 95% CI as compared to those with less than 10%
density.5
 Age at menarche and menopausal age
Menarche, the time of commencement of menstrual cycles, is characterised by
monthly fluctuations in hormone levels, ovulation and cellular proliferation in the
breast. The breast actually begins to develop 1–2 years before menarche and, during the
time of early adolescence, breast tissue grows rapidly. In this relatively immature state,
 the breast epithelial cells are considered vulnerable to carcinogens and random errors
in the genetic material that can be passed on to additional breast cells as they divide.
During menopause, in addition to the gradual cessation of ovarian hormone production,
a process called involution occurs in the breast; this process is characterised by
decreased cell proliferation and an eventual reduction in the proportion of epithelial
cells. Breast cancer risk increased by a factor of 1·050 (95% CI 1·044–1·057;
p<0·0001) for every year younger at menarche, and independently by a smaller amount
(1·029, 1·025–1·032; p<0·0001), for every year older at menopause. Premenopausal
women had a greater risk of breast cancer than postmenopausal women of an identical
age (RR at age 45–54 years 1·43, 1·33–1·52, p<0·001).7
 Parity
Parous women had lower risk of ER+ breast cancer but not ER- breast cancer as
compared to nulliparous with odd ratio 0.82 at 95% CI.6 The protective effect of parity
is thought to be due to permanent changes that occur in the breast epithelial cells during
the third trimester. in preparation for lactation. These more mature (ie differentiated)
cells are thought to be less vulnerable to DNA damage that might lead to cancer; hence,
breast cancer risk during the years following a full-term pregnancy is reduced.
 Breastfeeding
Breastfeeding reduces risk of breast cancer, probably through several mechanisms,
including differentiation of the epithelial cells, reduction in the cumulative number of
ovulatory cycles due to delay in re-establishing ovulation after a completed pregnancy
and the reduction of epithelial cells following completion of breastfeeding Among
parous women, breastfeeding was associated with lower risk of ER− breast cancer as
compared to never breastfed with odd ratio 0.82 at 95% CI, but not ER+ breast cancer.6
 Menstruation cycle length
Overall, women with long menstrual cycles at ages 18 to 22 years (>32 days or too
irregular to estimate) did not experience a significantly lower breast cancer risk
compared with women with normal cycle lengths (26-31 days) at that age [covariate-
adjusted hazard ratio (HR), 0.92; 95% confidence interval (95% CI), 0.79-1.06].
Among women ages <40 years, those with menstrual cycles lasting >32 days or too
irregular to estimate at ages 18 to 22 years had a decreased incidence of breast cancer
(covariate-adjusted HR, 0.71; 95% CI, 0.53-0.97).8
1. Van Seijen M, Lips EH, Thompson AM, et al. Ductal carcinoma in situ: to treat or
not to treat, that is the question. Br J Cancer. 2019;121(4):285–292.
doi:10.1038/s41416-019-0478-6
2. Mao K, Yang Y, Wu W, Liang S, Deng H, Liu J. Risk of second breast cancers after
lobular carcinoma in situ according to hormone receptor status. PLoS One.
2017;12(5):e0176417. Published 2017 May 3. doi:10.1371/journal.pone.0176417
3. Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC et al., Benign Breast
Disease and the Risk of Breast Cancer. N Engl J Med. 2005; 353:229-237
4. Cote MT, Ruterbusch JJ, Alosh B, Bandyopadhyay S, Kim E, Albashiti B, et al.
Benign Breast Disease and the Risk of Subsequent Breast Cancer in African
American Women. Canc Prevent Res. 2012; 5(12): 1375-1380
5. Boyd NF, Martin LJ, Yaffe MJ, Minkin S. Mammographic density and breast
cancer risk: current understanding and future prospects. Breast Cancer Res. 2011;
13(223).
6. Fortner RT, Sisti J, Chai B, Collins L, Rosner B, et al. Parity, breastfeeding, and
breast cancer risk by hormone receptor status and molecular phenotype: results from
the Nurses’ Health Studies. Biomed Central. 2019; 21(40).
7. Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause,
and breast cancer risk: individual participant meta-analysis, including 118 964
women with breast cancer from 117 epidemiological studies. Lancet Oncol.
2012;13(11):1141–1151. doi:10.1016/S1470-2045(12)70425-4
8. Terry KL, Willett WC, Rich-Edwards JW, Hunter DJ, Michels KB. Menstrual cycle
characteristics and incidence of premenopausal breast cancer. Cancer Epidemiol
Biomarkers Prev. 2005;14(6):1509–1513. doi:10.1158/1055-9965.EPI-05-0051