No Abstract.  South African Family Practice Vol. 47(6) 2005: 48-5

Guidozzi, F

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SA Fam Pract 2005;47(6)48ReviewWhat are the risks for breastcancer?Although breast cancer occurs 100times more frequently in females thanin males, suggesting that breastcancer prefers tissue that is primedby female hormones, there are asignificant number of other risk factorsthat are associated with its occurrence.These risk factors have cast doubt onthe role of the sex hormones beingprimarily responsible for the initiationof breast cancer, namely:a) The disease is more commonlydiagnosed in post-menopausalwomen not on HRT than in pre-menopausal women.b) It is a disease of the ageing.  Theolder the woman, the more likelyshe is to develop breast cancer.At age 50 years, the rate ofdiagnosis is 1:50, whereas at 70years, it is 1:20 and at 85 years itis 1:10.  A 50 year old has a 10%lifetime probability of developingand a 3% probability of dying ofbreast cancer.c) Pregnancy before the age of 25years, even though associated withhigh levels of endogenous sexhormones, results in a reducedrisk, especially if associated withbreast-feeding.d) An increas ing number  o fpregnancies is also associatedwith a reduction.  Women who have5 or more children have about two-thirds the rate of breast cancer aswomen who have one child.e) The oral combined contraceptivepill is not associated with anincreased diagnosis of breastcancer.f) A body mass index of greater than30 kg/m2 , or regular consumptionof alcohol, will increase theincidence of breast cancer.g) A menarche <12 years ormenopause >54 years areassociated with an increasedincidence.h) Increased breast density at thetime of mammography.  Recentreviews of 7 studies have indicateddecreased mammographicsensitivity in hormone users, witha slight increase in false positiverecalls.  Post-menopausal womennot on HRT, but with an increasedbreast density on mammography,require mandatory surveillance withannual mammography andultrasonography as these patientsmay have a higher incidence ofbreast cancer.i) A family history of two first degreefamily relatives with breast cancerdoubles the individual’s risk ofdeveloping the disease.  Familyhistory does not further increasethe small risk of breast cancer saidto be associated with HRT usage.j) Oophorectomy before 35 yearsreduces the lifetime risk of breastcancer by 75% in women.The Women’s Health Initiative study(WHI) found that, in women who weretak ing  con t i nued  es t rogen -progestogen therapy, there was a 26%increase in invasive cancer.  In thisstudy, only a quarter of the participantshad prior HRT use and the averageparticipant’s age was 63 years.  Therecently published data from theestrogen-only arm of the WHI did notshow any increased risk for thedevelopment of breast cancer.A synopsis of the currently heldviews is as follows:a) Estrogen alone does not appearto increase the incidence of breastcancer.b) Estrogen-progestogen combina-tions, are either associated with asmall increase in the risk of breastcancer or, in fact, promote pre-existing tumour rather than initiatingthe tumour.c) The increase in risk is seen onlyafter 5 years of usage and not ifused <5 years.  The increase isonly of invasive cancers and notof in-situ or non-invasive lesions.d) This increase is only seen in pastusers and the effect is lost oncethe woman has stopped takingHRT for 5 years.e) In terms of absolute increase innumber of breast cancer per 1000women who commence HRT at theage of 50 years, and use it for 5,10 and 15 years respectively, theexcess of breast cancers will be2, 6 and 12.  The absolute increasein the WHI was 8 per 10 000women users per year.f) From the observational studies, itappears that higher doses andlonger duration of usage will impacton risk.  Hence the need to use thelowest dose of HRT which iseffective in controlling symptoms.g) Risk estimates for breast cancerwith HRT use are similar in theHERS I, HERS II, WHI and someobservational studies.  Forexample, the hazard ratio of 1.26reported by the WHI is consistentwith the risk ratio of 1.27 reportedafter 6.8 years of follow-up in HERSI/HERS II.  These data suggest thatbreast cancer risk may beincreased with long-term HRT use,but if this is so, the increase in riskis small.Will Hormone Therapy causebreast cancer?Over 50 epidemiological studies andsix meta-analyses have examined theassociation between hormone therapyand breast cancer risk in the past 30years, and the lack of a uniformGuidozzi F, MBBCh, FCOG, MROCOGHead of the Department of Obstetrics and GynaecologyFaculty of Health ScienceWits Medical SchoolCorrespondence: guidozzif@medicine.wits.ac.za(SA Fam Pract 2005;47(6): 48-50)Breast cancer and HRTSA Fam Pract 2005;47(6)50Reviewconsistent conclusion means that anyeffect, if at all, has to be a small one. Among studies that examinedestrogen-only use, 82% found no effecton breast cancer risk, 13% reporteda modest increase in risk, whilst 5%reported a reduced risk.  Results ofstudies with estrogen and progestogenpreparations followed a similar trend:80% found no effect, 10% reportedan elevated risk and 10% a reducedrisk.  The Collaborative Group onHormonal Factors in Breast Cancerreanalysed 90% of the worldwideepidemiological evidence on therelationship between risk of breastcancer and use of HRT.  The relativerisk for ever-users was 1.14, for currentor recent users 1.21, for current orrecent users with 5 or more years ofuse 1.35, and the relative risk for pastusers was 1.07.  The more recentlypublished randomised studies, HERSI, HERS II and the WHI, have beenaddressed above.  They all concurwith the observational data – there isa small increase in risk, but only afterapproximately 5 years of usage.What are the characteristicsof breast cancer that developswhilst taking HRT?From the mid 90s it became apparentfrom the observational studies that,even though there was this smallincrease of breast cancer in HRTusers, as described above, there wasan accompanying decreased mortalityfrom breast cancer in these patients.There is substantial evidence, froma number of studies, to support thatwomen taking HRT, when their breastcancers were diagnosed, had smallersized tumours, that were betterdifferentiated, had a higher localrestriction with less lymph nodeinvolvement.  They were more likelyto be lobular cancers, while the riskfor the more aggressive ductal cancersremained essentially constant.  Womenwho had an early menopause (<40years) had the greatest benefit fromHRT preventing fatal breast cancer.Although this is the commonly heldgeneral opinion, the WHI’s findingswere contradictory.  The authors didnot detect any differences in thehistologic types of breast cancer andin their study there was an earlierappearance of less differentiatedtumour.  The authors of the study,however, do point out that, althoughthe results were consistent withstimulation of growth in establishedbreast cancers, they were of theopinion that the delay in diagnosingthese tumours may have led to thisgreater number of less differentiatedtumours than described in previousstudies.  The latter they ascribe to thela rger  number  o f  abnorma lmammograms in the HRT group thanin the placebo group. The majority ofthe studies, including the WHI, haveall shown substantially improvedsurvival rates in women with breastcancer whilst on HRT. In the WHI,despite the greater likelihood of lessdifferentiated tumours, there was notan accompanying increase in mortality.Continuous combined HRT willlead to increased breast density inapproximately 35% of patients,sequential combined HRT in  15% andestrogen alone in  10% of users.  DoesHRT  impa i r  mammograph icscreening?  Overall, the studiessuggest a decreased mammographicsensitivity, but with little impact onspecificality. Even though theeffectiveness of the breast cancerscreening may be somewhat reduced,the outcome has not had adverseimpact on breast cancer mortality.The increase in breast densityassociated with postmenopausal HRTappears to be a transient, reversiblechange, a change unlikely to have apers is tent  e f fect  on cel lu larproliferation.  After discontinuation ofHRT, breast density rapidly decreases. Two weeks of cessation allowsregression of HRT induced density.Therefore, there is good reason torecommend discontinuation of HRTfor two weeks prior to mammographyin all women older than 65 years whohave dense breasts and in all youngerwomen who have been recalledbecause of a suspicious or abnormalmammogram.  The general consensusat present is that breast cancersdiagnosed in HRT users are betterdifferentiated, of lower grade andstage, with better outcomes.The contrary finding in the WHImay reflect the older age of itsparticipants and certainly does notreceive any support from any otherstudy. References: Available on request.

Breast cancer and HRT

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Breast cancer and HRT

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