Martha Hickey

Breast cancer in young women and its impact on reproductive function

BACKGROUND Breast cancer is the most common cancer in women in developed countries, and 12% of breast cancer occurs in women 20–34 years. Survival from breast cancer has significantly improved, and the potential late effects of treatment and the impact on quality of life have become increasingly important. Young women constitute a minority of breast cancer patients, but commonly have distinct concerns and issues compared with older women, including queries regarding fertility, contraception and pregnancy. Further, they are more likely than older women to have questions regarding potential side effects of therapy and risk of relapse or a new primary. In addition, many will have symptoms associated with treatment and they present a management challenge. Reproductive medicine specialists and gynaecologists commonly see these women either shortly after initial diagnosis or following adjuvant therapy and should be aware of current management of breast cancer, the options for women at increased genetic risk, the prognosis of patients with early stage breast cancer and how adjuvant systemic treatments may impact reproductive function. METHODS No systematic literature search was done. The review focuses on the current management of breast cancer in young women and the impact of treatment on reproductive function and subsequent management. With reference to key studies and meta-analyses, we highlight controversies and current unanswered questions regarding patient management. RESULTS Chemotherapy for breast cancer is likely to negatively impact on reproductive function. A number of interventions are available which may increase the likelihood of future successful pregnancy, but the relative safety of these interventions is not well established. For those who do conceive following breast cancer, there is no good evidence that pregnancy is detrimental to survival. We review current treatment; effects on reproductive function; preservation of fertility; contraception; pregnancy; breastfeeding and management of menopausal symptoms following breast cancer. CONCLUSION This paper provides an update on the management of breast cancer in young women and is targeted at reproductive medicine specialists and gynaecologists.

The fertility-related concerns, needs and preferences of younger women with breast cancer: a systematic review

Breast cancer is the most commonly diagnosed type of cancer in reproductive aged women. Adjuvant systemic therapy is recommended in most women and has been demonstrated to reduce the risk of recurrence and increase survival. However, there may be a negative impact of adjuvant systemic therapy on fertility as well as on subsequent quality of life. There are a number of fertility preservation options currently available and relevant information regarding these options should be provided prior to commencing adjuvant treatment. The aim of the review is to identify the fertility-related needs, concerns and preferences of young women with early breast cancer. The databases MEDLINE and EMBASE were searched from 1988 onwards using keywords, and examining reference lists. Of the 499 articles identified, 20 met eligibility criteria and were reviewed. Multiple fertility-related information needs specific to this group regarding menstrual changes and potential infertility attitudes to, and actual decisions made regarding, pregnancy breastfeeding and contraception emerged. Information on fertility-related decisions was rated as important, and the preferred methods for obtaining this information was consultation with a specialist or a decision aid early in the treatment plan. There is limited research about fertility-related needs, and even less on contraceptive preferences and the attitudes of health care providers towards fertility-related issues. No studies describing the development of tools to assist with decisions about fertility-related choices were identified. Young women with early breast cancer have specific fertility- and menopause-related needs and concerns, which are commonly not adequately addressed or discussed prior to commencing adjuvant therapy.

Treatment of menopausal symptoms: what shall we do now?

During the past few years, many women and doctors have revised their opinions of hormone replacement therapy (HRT) for menopausal symptoms, and a substantial number of individuals have discontinued its use because of concerns about side-effects. Numerous alternatives to HRT are promoted, and assessment of the quality of evidence about the safety and effectiveness of these compounds can be difficult. In this Review, we summarise the data from studies addressing the efficacy, risks, and benefits of frequently prescribed treatments, and offer evidence-based clinical guidelines for the management of menopausal symptoms. Although few comparative studies exist, oestrogen alone or combinations of oestrogen and progestagen are likely to be the most effective treatments for menopausal hot flushes and vaginal dryness. Tibolone is as effective as HRT, however, and might also improve libido. For those who wish to avoid hormonal treatments, there are few effective options. Selective serotonin reuptake inhibitors might be effective in the very short term (less than 12 weeks) and are well tolerated. There is not enough evidence that any of the complementary therapies available are any better than placebo for menopausal vasomotor symptoms, and few safety data exist.

It's Now or Never: Fertility-Related Knowledge, Decision-Making Preferences, and Treatment Intentions in Young Women With Breast Cancer—An Australian Fertility Decision Aid Collaborative Group Study

PURPOSE For many young women with early breast cancer, fertility is a priority. Interventions to retain fertility options generally need to be accessed before chemotherapy, but many women do not receive information regarding these options in a timely fashion. Knowledge about fertility and decisional conflict has not previously been measured in young patients with breast cancer considering future pregnancies. METHODS One hundred eleven young women with early breast cancer who had not yet completed their families were recruited around the time of diagnosis. Knowledge regarding fertility-related information, decisional conflict, and preferences regarding fertility information and decision making was measured. RESULTS From a potential fertility-related knowledge score of 10, the mean was 5.2 (standard deviation = 2.3; range, 0 to 10). Decreased knowledge was associated with increased decisional conflict about pursuing fertility preserving interventions (odds ratio [OR] = 0.57; 95% CI, 0.44 to 0.73; P < .001). Thirty-one percent of women reported that they would consider undertaking in vitro fertilization (IVF) as a method to conserve their fertility, whereas 38% were uncertain. Consideration of IVF was not related to whether subjects were in a committed relationship (OR = 1.20; P = .716) or a definite desire for more children (OR = 1.54; P = .513). CONCLUSION Around diagnosis, many young patients with breast cancer have low levels of knowledge about fertility issues. Further, low knowledge is associated with increased decisional conflict, which is likely to undermine the quality of decision making. These findings suggest that targeted and timely fertility information may reduce decisional conflict and increase informed choice. Neither relationship status nor firm plans regarding future children reliably predict desire to pursue fertility preservation.

The Relationship between Maternal and Umbilical Cord Androgen Levels and Polycystic Ovary Syndrome in Adolescence: A Prospective Cohort Study

CONTEXT The prenatal antecedents of polycystic ovary syndrome (PCOS) are not known, but prenatal androgen exposure is thought to contribute. This has not previously been investigated in large prospective studies of normal human pregnancy. OBJECTIVE The aim of the study was to establish the prospective relationship between early life androgen exposure and PCOS in adolescence. DESIGN AND SETTING A prospective cohort study was conducted in the general community. PATIENTS OR OTHER PARTICIPANTS A total of 2900 pregnant women were recruited at 18 wk gestation. Prenatal androgen exposure was measured from maternal blood samples (at 18 and 34-36 wk) and umbilical cord blood. Timed (d 2-5 menstrual cycle) blood samples were collected, clinical hyperandrogenism was assessed, and transabdominal ultrasound examination of ovarian morphology was performed in 244 unselected girls from the Raine cohort aged 14-17 yr. MAIN OUTCOME MEASURE(S) We examined the relationship between early life androgen exposure and PCOS in adolescence. RESULTS We did not observe a statistically significant relationship between early life androgen exposure and PCOS in adolescence. CONCLUSIONS This is the first prospective study to evaluate the relationship between prenatal androgen exposure and PCOS in adolescence in normal pregnancy. Our findings do not support the hypothesis that maternal androgens, within the normal range for pregnancy, directly program PCOS in the offspring.

Menopausal hot flushes and night sweats: where are we now?

ABSTRACT Objective An overview of the current knowledge on the etiology and treatment of vasomotor symptoms in postmenopausal women. Materials and methods Acknowledged experts in the field contributed a brief assessment of their areas of interest which were combined and edited into the final manuscript. Results Women around the world experience vasomotor symptoms as they enter and complete the menopause transition. Vasomotor symptoms, specifically hot flushes, are caused by a narrowing of the thermoneutral zone in the brain. This effect, although related to estrogen withdrawal, is most likely related to changes in central nervous system neurotransmitters. Peripheral vascular reactivity is also altered in symptomatic women. Estrogen replacement therapy is the most effective treatment for hot flushes. Of the other interventions investigated, selective serotonin and selective norepinephrine reuptake inhibitors and gabapentin show efficacy greater than placebo. Objective monitoring of hot flushes indicates a robust improvement with hormone replacement therapy but little to no change with placebo. These data suggest that the subjective assessment of responses to therapy for vasomotor symptom results in inaccurate data. Hot flushes have recently been associated with increased cardiovascular risks and a lower incidence of breast cancer, but these data require confirmation. Conclusions Vasomotor symptoms are experienced by women of all ethnic groups. They are caused by changes in the central nervous system associated with estrogen withdrawal and are best treated with estrogen replacement therapy. Objective monitoring of hot flushes indicates that placebo has little to no effect on their improvement. Subjective assessments of hot flushes in clinical trials may be inaccurate based on objective measurement of the frequency of hot flushes. Based on preliminary reports, women experiencing hot flushes have an increased risk of cardiovascular disease and a reduced incidence of breast cancer.

Clinical, ultrasound and biochemical features of polycystic ovary syndrome in adolescents: implications for diagnosis

BACKGROUND Diagnosing polycystic ovary syndrome (PCOS) in adolescence is clinically challenging. The prevalence of clinical, ultrasound and biochemical features of PCOS in a community-based adolescent population using current diagnostic criteria has not previously been described. METHODS This was a prospective cohort study with 244 unselected post-menarchal girls, mean age 15.2 years, of whom 91% were Caucasian. Subjects were recruited from a large population-based birth cohort (the Raine cohort). Clinical hyperandrogenism (HA) was quantified using Ferriman-Gallwey scores. In the early follicular phase (Day 2-6), we measured circulating androgens and sex hormone-binding globulin by immunoassay, and ovarian morphology was assessed by transabdominal ultrasound examination. BMI and waist-hip ratio were measured. RESULTS Normal ranges for early follicular phase androgens in adolescence were derived for this population. The top 5 and 10% of circulating free testosterone levels were 45.6 and 34.5 pmol/l, respectively. Fifty-one percent of girls reported menstrual irregularity. Clinical HA was uncommon, being observed in only 3.5% of girls. Mean ovarian volume was greater than that reported by others in adult women and 35% of girls had polycystic ovary morphology on transabdominal ultrasound. Taking the upper 5% of free testosterone as HA, 42 girls (18.5%) would have met the Rotterdam criteria for PCOS, 11 girls (5%) the Androgen Excess Society criteria and 7 girls (3.1%) the National Institutes of Health criteria. CONCLUSIONS Menstrual irregularity is common in adolescence and does not relate to clinical or biochemical HA. Diagnostic criteria for PCOS which include ovarian volume and morphology may be of limited use in adolescence.

Practical clinical guidelines for assessing and managing menopausal symptoms after breast cancer

BACKGROUND The purpose of this study was to provide practical, evidence-based guidelines for evaluating and treating common menopausal symptoms following breast cancer. METHODS Literature review of the causes, assessment and management of menopausal symptoms in breast cancer patients. RESULTS A number of nonhormonal treatments are effective in treating hot flashes. Whether pharmacological treatment is given will depend on the severity of symptoms and on patient wishes. For severe and frequent hot flashes, the best data support the use of venlafaxine, paroxetine and gabapentin in women with breast cancer. Side-effects are relatively common with all these agents. For vaginal dryness, topical estrogen treatment is the most effective but the safety of estrogens following breast cancer is not established. There are limited data on effective treatments for sexual dysfunction during menopause. CONCLUSION Menopausal symptoms after breast cancer should be evaluated and managed as warranted using a systematic approach and may benefit from multidisciplinary input.

Making hard choices easier: a prospective, multicentre study to assess the efficacy of a fertility-related decision aid in young women with early-stage breast cancer

Background:Fertility is a priority for many young women with breast cancer. Women need to be informed about interventions to retain fertility before chemotherapy so as to make good quality decisions. This study aimed to prospectively evaluate the efficacy of a fertility-related decision aid (DA).Methods:A total of 120 newly diagnosed early-stage breast cancer patients from 19 Australian oncology clinics, aged 18–40 years and desired future fertility, were assessed on decisional conflict, knowledge, decision regret, and satisfaction about fertility-related treatment decisions. These were measured at baseline, 1 and 12 months, and were examined using linear mixed effects models.Results:Compared with usual care, women who received the DA had reduced decisional conflict (β=−1.51; 95%CI: −2.54 to 0.48; P=0.004) and improved knowledge (β=0.09; 95%CI: 0.01–0.16; P=0.02), after adjusting for education, desire for children and baseline uncertainty. The DA was associated with reduced decisional regret at 1 year (β=−3.73; 95%CI: −7.12 to −0.35; P=0.031), after adjusting for education. Women who received the DA were more satisfied with the information received on the impact of cancer treatment on fertility (P<0.001), fertility options (P=0.005), and rated it more helpful (P=0.002), than those who received standard care.Conclusion:These findings support widespread use of this DA shortly after diagnosis (before chemotherapy) among younger breast cancer patients who have not completed their families.

Implanon as a contraceptive choice for teenage mothers: a comparison of contraceptive choices, acceptability and repeat pregnancy.

BACKGROUND This study was conducted to compare the incidence of repeat teenage pregnancy over a 24-month period postpartum among users of Implanon, the combined oral contraceptive pill (COCP) or depot medroxyprogesterone acetate (DMPA) and barrier methods or nothing (barrier/none). Contraceptive continuation rates 24 months postpartum for Implanon and COCP/DMPA were also compared. STUDY DESIGN A prospective cohort study was conducted. Comparison groups were postpartum teenagers (12-18 years old) who self-selected Implanon (n=73), COCP/DMPA (n=40) and barrier/none (n=24). Questionnaires were used to gather data at recruitment and postpartum at 6 weeks and then 3 monthly intervals for 2 years. RESULTS At 24 months postpartum, 48 (35%) teenagers had conceived. Implanon users became pregnant later than other contraceptive groups (p=.022), with mean time to first repeat pregnancy of 23.8 months [95% confidence interval (CI), 22.2-25.5], compared to 18.1 months (95% CI, 15.1-20.7) for COCP/DMPA and 17.6 months (95% CI, 14.0-21.3) for barrier/none. Implanon users were more likely to continue their use at 24 months than COCP/DMPA (p<.001) users. The mean duration for Implanon users was 18.7 months (95% CI, 17.0-20.3) compared to 11.9 months (95% CI, 9.5-14.3) for COCP/DMPA. CONCLUSION Teenagers who choose Implanon are significantly less likely to become pregnant and were found to continue with this method of contraception 24 months postpartum compared to those who choose COCP or DMPA and barrier methods or nothing.