Regis­tered di­eti­cian and breast can­cer sur­vivor Ash­leigh Caradas ex­am­ines the ef­fects of can­cer treat­ments on fer­til­ity.

Living and Loving - - CONTENTS -

Hear­ing the words “You have can­cer” for the first time can feel like your fu­ture has been up­graded into a hur­ri­cane-in­duced dust storm. Hav­ing breast can­cer, in par­tic­u­lar, comes with ad­di­tional chaos and un­cer­tainty, be­cause it threat­ens so many things con­cern­ing your wom­an­hood. You not only face los­ing your breasts, your hair, your lashes and brows, but also your abil­ity to have chil­dren. Med­i­cal treat­ments for breast can­cer can also send you into med­i­cally in­duced early menopause.

Breasts can be re­con­structed and hair grows back, but the last­ing ef­fects on the fe­male hor­monal sys­tem can be par­tic­u­larly dev­as­tat­ing − es­pe­cially if you’re of child­bear­ing age. For­tu­nately, it’s not all doom and gloom and many women go on to start or ex­pand their fam­i­lies.

So far, sci­en­tific data and med­i­cal opin­ion point to the safety of preg­nancy af­ter breast can­cer, but will in­ter­rupt­ing a woman’s en­docrine ther­apy (treat­ment that adds, blocks or re­moves hor­mones) to pre­pare for preg­nancy in­crease her re­cur­rence risk? An In­ter­na­tional Breast Can­cer Study Group (IBCSG) trial, known as the POS­I­TIVE trial, is set­ting out to find the an­swers. The study, which is al­ready in full swing, in­tends to eval­u­ate the preg­nancy out­comes and safety of in­ter­rupt­ing en­docrine ther­apy for hor­mone re­cep­tor-pos­i­tive early stage breast can­cer among 500 women.

Why would you choose to in­ter­rupt en­docrine ther­apy in­stead of wait­ing un­til treat­ment is fin­ished? For early stage hor­mone re­cep­tor-pos­i­tive breast can­cer, en­docrine ther­a­pies are tra­di­tion­ally pre­scribed for five years

(with 10 years rec­om­mended in some cases). If you’re di­ag­nosed in your 20s, for ex­am­ple, you have more time, but if you’re di­ag­nosed in your late 30s or early 40s, you might be ad­vised to pause treat­ment in or­der to be­come preg­nant be­fore your age causes fer­til­ity is­sues. The longer a woman un­der­goes hor­mone ther­a­pies, the greater the risk of ad­di­tional fer­til­ity dam­age.

Ac­cord­ing to Dr Carol Benn from the Breast Care Cen­tre at Mil­park hos­pi­tal in Jo­han­nes­burg, “There is no ev­i­dence for an in­creased risk of dis­ease re­cur­rence as­so­ci­ated with most fer­til­ity preser­va­tion meth­ods and preg­nancy,” but data is still rel­a­tively sparse. “Con­ven­tional wis­dom says to wait un­til the pa­tient gets through the pe­riod of high­est risk re­cur­rence.” For most pa­tients, this is con­sid­ered the first two years af­ter start­ing en­docrine ther­apy.

The ef­fects

Ac­cord­ing to Dr Benn, all the main breast can­cer ther­a­pies, es­pe­cially chemo­ther­apy, do af­fect fer­til­ity.

Side ef­fects in­clude dam­age or de­struc­tion of your eggs, go­ing into early menopause and a com­pro­mised abil­ity to carry your baby to term.

She ex­plains that with chemo­ther­apy, the ovaries be­come sen­si­tised to the drugs. In nor­mal pre­menopausal ovaries, there is a low re­cruit­ment of pri­mor­dial egg-con­tain­ing fol­li­cles, but when they are ex­posed to chemo­ther­apy, there is a de­crease in ovar­ian hor­mones (estra­diol and FSH) re­sult­ing in an in­crease in fol­lic­u­lar re­cruit­ment and more eggs be­ing at risk of dam­age. In other words, your ovar­ian re­serves will be sig­nif­i­cantly de­pleted by the time chemo­ther­apy is com­pleted, leav­ing you with fewer vi­able eggs.

For this rea­son, chemo­ther­apy of­ten re­sults in early menopause, which can mean in­fer­til­ity. But not all women ex­pe­ri­ence menopause af­ter chemo­ther­apy. In one study of 286 pre-menopausal Chi­nese women who un­der­went chemo­ther­apy for breast can­cer, pub­lished in 2016 in PLOS One, most women lost their pe­ri­ods af­ter chemo­ther­apy, but only 50% de­vel­oped chemo­ther­apy-re­lated menopause.

Ac­cord­ing to Dr Benn, ad­di­tional ther­a­pies for breast can­cer, which in­volve fol­low-up treat­ments of ta­mox­ifen or ovar­ian sup­pres­sion to en­hance the ef­fect of chemo­ther­apy or ra­di­a­tion, do not ap­pear to cause per­ma­nent amen­or­rhea (loss of pe­riod) or in­fer­til­ity. How­ever, en­docrine ther­apy usu­ally en­tails years of treat­ment with preg­nancy con­traindi­cated. Age­ing over the pe­riod of treat­ment will com­pro­mise the woman’s fer­til­ity even if the treat­ment does not.

Fer­til­ity preser­va­tion

Depend­ing on the na­ture of the di­ag­no­sis, some women are sent straight to the chemo­ther­apy room with­out much time to con­sider fer­til­ity op­tions. Oth­ers, like those who are not pre­scribed chemo­ther­apy or are hav­ing surgery (such as a lumpec­tomy or mas­tec­tomy) be­fore start­ing other

‘There is no ev­i­dence for an in­creased risk of dis­ease re­cur­rence as­so­ci­ated with most fer­til­ity preser­va­tion meth­ods and preg­nancy.’

treat­ments, have a grace pe­riod in which to con­sider their op­tions. Fer­til­ity preser­va­tion op­tions are gen­er­ally dis­cussed by the on­col­o­gist and a fer­til­ity spe­cial­ist and weighed in terms of the risks, which in­clude fu­elling can­cer growth by stim­u­lat­ing the ovaries for egg har­vest­ing.

Ac­cord­ing to a re­view of fer­til­ity preser­va­tion op­tions in breast can­cer pa­tients, pub­lished in Gyne­co­log­i­cal En­docrinol­ogy in 2015, cur­rent fer­til­ity preser­va­tion op­tions range from well-es­tab­lished tech­niques to more ex­per­i­men­tal in­ter­ven­tions. Most com­monly, ovar­ian stim­u­la­tion be­fore chemo­ther­apy is ini­ti­ated, tak­ing into ac­count the hor­mone sta­tus of the par­tic­u­lar can­cer. Cry­op­reser­va­tion of ei­ther oocytes (eggs) or em­bryos are the most suc­cess­ful fer­til­ity preser­va­tion meth­ods. You can choose to freeze just your eggs, which is of­ten the case if you’re sin­gle, or to fuse the egg with sperm to form an em­bryo. How­ever, not all on­col­o­gists will al­low ovar­ian stim­u­la­tion be­fore chemo­ther­apy − es­pe­cially in fast­grow­ing can­cers. In these cases, fer­til­ity op­tions will be con­sid­ered depend­ing on the na­ture of the tu­mour.

Ac­cord­ing to the study, an­other more ex­per­i­men­tal method is ad­min­is­ter­ing a GnRH (hu­man go­nadotropin­re­leas­ing hor­mone) ag­o­nist dur­ing chemo­ther­apy, which helps min­imise dam­age to the eggs by sup­press­ing the ovaries. A 2018 anal­y­sis of mul­ti­ple stud­ies and look­ing at 873 pa­tients, pub­lished in the Jour­nal of Clin­i­cal On­col­ogy, looked at the use of ovar­ian sup­pres­sion dur­ing chemo­ther­apy and found GnRH was both safe and ef­fi­cient in pre­vent­ing ovar­ian dam­age dur­ing chemo­ther­apy and may po­ten­tially im­prove fu­ture fer­til­ity in pre-menopausal pa­tients with early breast can­cer.

An­other ex­per­i­men­tal method, de­vel­oped in Is­rael, takes slices of the pre-menopausal ovary and pre­serves them for later use. The ovar­ian tis­sue is then re­con­nected to the ovary when the woman is ready to try and con­ceive. The process, known as ovar­ian cry­op­reser­va­tion, is rel­a­tively new and fur­ther stud­ies are needed to pro­duce re­li­able data. A 2018 re­view study in the Jour­nal of Gyne­col­ogy, Ob­stet­ric and Hu­man Re­pro­duc­tion looked at cases from 2000 to 2017 and found that in 16 pub­lished cases of ovar­ian trans­plants among pa­tients treated for breast can­cer, there were 14 preg­nan­cies, 11 births and three fail­ures.

Safety con­sid­er­a­tions

Some on­col­o­gists will not al­low egg stim­u­la­tion be­fore chemo­ther­apy. Ac­cord­ing to Dr Chris Ven­ter, a fer­til­ity spe­cial­ist at Vi­taLab fer­til­ity clinic in Jo­han­nes­burg, stim­u­la­tion of ovaries to re­trieve eggs will post­pone the chemo­ther­apy for a max­i­mum of 10 to 12 days. This should, in the ma­jor­ity of cases, not change the prog­no­sis of the pa­tient. He ex­plains that due to the high lev­els of oe­stro­gen dur­ing stim­u­la­tion, women with oe­stro­gen re­cep­tor­pos­i­tive breast can­cer could face a risk of dis­ease pro­gres­sion. How­ever, ev­i­dence has shown that adding the drug Letro­zole (an aro­matase in­hibitor that re­duces the amount of oe­stro­gen avail­able to tu­mours) re­duces the risk of dis­ease pro­gres­sion. GnRH ag­o­nists have some the­o­ret­i­cal risks and are as­so­ci­ated with side ef­fects, in­clud­ing bone loss and menopausal symp­toms. How­ever, ac­cord­ing to cur­rent re­search, the method is safe for use in breast can­cer pa­tients and there is no risk of dis­ease pro­gres­sion with ovar­ian cry­op­reser­va­tion.

Con­cep­tion time

In the POS­I­TIVE trial, once a woman has com­pleted the min­i­mum re­quire­ments of her en­docrine ther­apy, she can stop and wait three months be­fore at­tempt­ing to fall preg­nant.

While it is pos­si­ble to fall preg­nant dur­ing this pe­riod, there isn’t a huge amount of time to keep try­ing. For safety, the POS­I­TIVE trial of­fers up to two years in­ter­rup­tion of en­docrine ther­apy to al­low preg­nancy, de­liv­ery, breastfeeding, or fail­ure to con­ceive.

For women who can’t fall preg­nant nat­u­rally, in vitro fer­til­i­sa­tion (IVF) or an al­ter­na­tive fer­til­ity method might be in­di­cated. If you al­ready have eggs or em­bryos frozen, you can use these. If you did not do any fer­til­ity preser­va­tion prior to treat­ment, ovar­ian stim­u­la­tion will be re­quired.

Ac­cord­ing to both Dr Benn and Dr Ven­ter, these treat­ments do not in­crease breast can­cer in­ci­dence. Re­sults from a new long-term study in JAMA in­di­cated that un­der­go­ing fer­til­ity treat­ment with IVF did not in­crease the risk for breast can­cer, com­pared with other fer­til­ity treat­ments or with women in the gen­eral pop­u­la­tion.

Dr Ven­ter ex­plains that af­ter can­cer treat­ment, the pa­tient needs to see a re­pro­duc­tive spe­cial­ist to de­ter­mine her nat­u­ral fer­til­ity. The chances will be dic­tated mainly by a pa­tient’s age, her egg re­serve and other fac­tors like the qual­ity of her part­ner’s sperm. It is bet­ter to have a plan and set some time­lines. If the prog­no­sis is good, try­ing to con­ceive nat­u­rally would be the pre­ferred route and to move on to as­sisted re­pro­duc­tive tech­niques.

Ul­ti­mately, the de­ci­sion to un­dergo fer­til­ity preser­va­tion, or to stop treat­ment and to try for chil­dren, is a per­sonal one that should be made in con­junc­tion with a va­ri­ety of spe­cial­ists. Although many women will be­come in­fer­tile af­ter breast can­cer, mod­ern med­i­cal ad­vances con­tinue to give hope to mil­lions.

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