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Journal of Clinical Oncology, Vol 22, No 20 (October 15), 2004: pp. 4174-4183 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.01.159 Web-Based Survey of Fertility Issues in Young Women With Breast CancerFrom the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA; and Young Survival Coalition, New York, NY Address reprint requests to Ann H. Partridge, MD, MPH, Dana-Farber Cancer Institute, 44 Binney St, D1210, Boston, MA 02115; e-mail: ahpartridge{at}partners.org
PURPOSE: Young women with breast cancer often seek advice about whether treatment will affect their fertility. We sought to gain a better understanding of women’s attitudes about fertility and how these concerns affect decision making. PATIENTS AND METHODS: We developed a survey about fertility issues for young women with a history of early-stage breast cancer. The survey was e-mailed to all registered Young Survival Coalition survivor members (N = 1,702). E-mail reminders were used. RESULTS: Six hundred fifty-seven eligible respondents completed the survey. Mean age at breast cancer diagnosis was 32.9 years; mean current age was 35.8 years. Ninety percent of women were white; 62% were married; 76% were college graduates. Stages at diagnosis were as follows: 0, 10%; I, 27%; II, 47%; III, 13%. Sixty-two percent of women were within 2 years of diagnosis. Fifty-seven percent recalled substantial concern at diagnosis about becoming infertile with treatment. In multivariate logistic regression, greater concern about infertility was associated with wish for children/more children (odds ratio [OR], 120; P < .0001), number of prior pregnancies (OR, 0.78; P = .01), and prior difficulty conceiving (OR, 1.86; P = .08). Twenty-nine percent of women reported that infertility concerns influenced treatment decisions. Seventy-two percent of women reported discussing fertility concerns with their doctors; 51% felt their concerns were addressed adequately. Women seemed to overestimate their risk of becoming postmenopausal with treatment. CONCLUSION: Fertility after treatment is a major concern for young women with breast cancer. There is a need to communicate with and educate young patients regarding fertility issues at diagnosis and a need for future research directed at preserving fertility for young breast cancer survivors.
More than 11,500 women in their 20s and 30s are diagnosed with breast cancer each year in the United States.1 An additional 2,200 women in this age group are diagnosed with noninvasive disease. For these young women, and some older women, the impact of their breast cancer diagnosis and treatment on fertility may be of great concern. Adjuvant chemotherapy for breast cancer may render a premenopausal woman amenorrheic, either temporarily or permanently. Even those women who continue to have regular menstrual cycles after chemotherapy may be less fertile than women who have not received chemotherapy, or they may go through menopause earlier than they might have otherwise.2-4 Although standard endocrine therapies such as tamoxifen do not generally cause permanent infertility, they entail years of treatment during which time a pregnancy is contraindicated. There is also increased interest in ovarian suppression or ablation as a treatment for breast cancer5; several ongoing trials are assessing whether ovarian suppression may add to our current treatments. Thus fertility concerns may complicate the treatment decision-making process for young women with breast cancer. Premenopausal women with breast cancer often seek advice about whether they will become infertile after treatment, and for those who wish to bear children, whether a subsequent pregnancy will alter their risk of disease recurrence. Because breast cancer is responsive to various endocrine changes, there has been concern that continued menstrual cycling and/or pregnancy after breast cancer may worsen prognosis.6-15 Although the data regarding pregnancy after breast cancer are reassuring, the available studies are imperfect and concerns about a negative impact for some patients remain. There is no question, however, that many young women are interested in preserving their fertility and hope to have children after a diagnosis of breast cancer. There is little information available about women’s attitudes regarding fertility surrounding the diagnosis and treatment of breast cancer. The prevalence and degree of concern over these issues is unknown, and the clinical, sociodemographic, and psychologic factors that influence these concerns are unclear. The extent to which attitudes about fertility affect treatment decisions for young women is similarly unknown. There is evidence that younger women may experience greater psychosocial distress and more difficulty with adjustment to the diagnosis and treatment of breast cancer.16-21 One aspect of this may be related to anxiety about future infertility or premature menopause. We collaborated with the Young Survival Coalition (YSC)22 (www.youngsurvival.org) in an effort to better understand fertility concerns. The YSC, an international nonprofit network of breast cancer survivors and supporters specifically dedicated to the unique issues facing young women with breast cancer, serves as an advocacy group seeking to educate and raise awareness about breast cancer in young women. We surveyed YSC survivor members to understand their concerns and attitudes regarding fertility.
The objectives of this study were as follows: to determine the proportion of premenopausal women age
We developed and piloted a one-time survey about fertility issues for young women with a history of early-stage breast cancer. Pilot testing was performed in the Dana-Farber Breast Cancer Program. We also used two previously validated questionnaires for women to recall their psychologic state before and at diagnosis: the Lasry Fear of Recurrence Scale23 and the Hospitalized Anxiety and Depression Scale (HADS).24,25 A link to the revised survey was e-mailed to all registered YSC survivor members with a history of breast cancer (N = approximately 1,702 at the time of the survey, including some individuals without a history of breast cancer). Eligible members (women who were premenopausal and age 40 years or younger at diagnosis of breast cancer) were encouraged to complete the survey. E-mail reminders to nonresponders were used to maximize response rates. Preliminary findings26 were sent to survey respondents via e-mail as well as posted on the YSC Web site at study completion. The study received local institutional review board approval, and informed consent was obtained via the Internet from each respondent before responding to the survey. Logistic regression was used for univariate analyses to compare women who reported greater levels of concern about fertility with those who did not. We used multiple variable logistic regression modeling to predict more concern about fertility and whether fertility concerns impacted a woman’s treatment decisions. We used the Spearman rank correlation coefficient to assess the relationship between concern about fertility and concern about menopause.
A total of 1,702 members were invited to participate in the survey (Fig 1). Not all of these members were eligible for the survey because some had not had breast cancer or were older than 41 years of age at diagnosis. Eight hundred sixty women gave electronic informed consent and began the survey; however, 203 women were excluded from these analyses for the following reasons: screened out due to ineligibility (no history of breast cancer; n = 8), completed only a small portion of the survey (n = 120), hysterectomy and/or bilateral oophorectomy at diagnosis (n = 11), pregnancy at diagnosis (n = 32), age greater than 40 years (n = 15), stage IV disease (n = 19; two women fell into two exclusion categories). Therefore, 657 women were eligible for analysis. Of note, two women who did not respond to the question regarding the primary outcome were excluded from those analyses.
Responder Characteristics Responder characteristics are listed in Table 1. The mean age at breast cancer diagnosis was 32.9 years, and mean age when responding to the survey was 35.8 years. The vast majority of respondents was white (90%) and most were at least college graduates (76%). At diagnosis, 62% were married, 8% were living as married, 7% were divorced or separated, and 23% were never married. Sixty-five percent of women were working full-time at the time of diagnosis. Most respondents (60%) reported that after paying bills, they could afford special things, and 11% of women reported difficulty paying bills or having to cut back in order to pay bills.
When responding to the survey, the majority (62%) of women were 2 years from diagnosis. The distribution of stage of breast cancer at diagnosis was as follows: stage 0, 10%; I, 27%; II, 47%; III, 13%; unsure, 3%. Forty percent of women underwent breast-conserving surgery for their breast cancer. Few women (7%) reported any comorbidities at the time of their diagnosis. Forty-one percent had a first-degree relative with a history of breast or ovarian cancer, and 70% of women had a family history of any cancer in a first-degree relative.
Fertility History at Diagnosis
Psychologic State Women were asked to reflect on their psychologic state in the weeks before diagnosis in an effort to evaluate baseline levels of anxiety and depression (Table 2). Twenty-two percent of women recalled severe anxiety before diagnosis by scoring greater than 10 on the HADS anxiety subscale. Only 4% of women recalled severe depression symptoms as assessed by a score of  10 on the HADS depression subscale. When women were asked to reflect on their feelings at diagnosis, 56% of women reported that they had substantial fear of breast cancer recurrence, as indicated by a score greater than 10 on the Lasry Fear of Recurrence Scale.
Concern About Fertility In multivariate analysis, more concern about fertility at diagnosis was associated with wish to have more children (odds ratio [OR], 120; P < .0001), prior number of pregnancies (OR, 0.78; P = .01), and a history of prior difficulty conceiving (OR, 1.86; P = .08 for yes, and OR, 3.15; P= .0001 for not applicable, indicating that a woman had not tried to conceive previously) when forcing age at diagnosis and stage into the model. Nonsignificant variables included age at diagnosis, race, education, employment status, financial situation, comorbidity, anxiety or depression as measured on the HADS before diagnosis, family history of cancer, stage, perceived risk of recurrence, type of surgery, radiation therapy, prior treatment for infertility and prior difficulty conceiving, abortions, miscarriages, stillbirths, and prior tubal ligation.
Fertility Concerns and Treatment Decisions
Women were asked the minimal decrease in absolute risk of recurrence that they would have been willing to accept from chemotherapy, given that adjuvant chemotherapy might reduce the chances of a future pregnancy and result in other side effects (Table 3). Women who reported greater concern about fertility required greater risk reduction from chemotherapy than women who were less concerned about fertility (P < .05). Women were also asked about the maximum risk of infertility that they would have accepted from a course of chemotherapy. Women who were more concerned about fertility were much less likely to accept a higher risk of infertility from adjuvant chemotherapy (P < .0001), although 57% of women who reported great concern were willing to accept a risk of infertility of 50%. Concern about menopause was significantly correlated with concern about infertility (Spearman rank correlation coefficient = 0.57; P < .0001). However, a substantial minority (36%) of women who reported less concern about infertility were concerned about going through menopause with treatment. For 11% of these women, menopausal concerns impacted on their treatment decisions (Table 3). Women were also asked to what extent they questioned the decisions they made about their breast cancer treatment at the time of the survey. Forty-five percent of all respondents questioned their treatment decisions, although most questioned their decisions only a little (Table 3). Those who were more concerned were not more likely to question their decision (P = .28). However, 33% of the women who were more concerned about fertility reported that such questioning was related to fertility issues, at least to some degree, compared with 8% of the women who were less concerned about fertility at diagnosis.
Attention to Fertility Issues and Risk Perceptions Women were asked to estimate how likely they had thought breast cancer treatment would make them go through menopause when they were making treatment decisions (Fig 2). Seventy-six percent of all respondents indicated that their chance of becoming postmenopausal with treatment was greater than 10%, and 56% felt their risk was greater than 40%. Nearly 50% of women age 30 years or younger at diagnosis reported that they perceived a greater than 40% chance of entering menopause with therapy. Risk perceptions varied significantly with age, with younger women estimating lower risk of treatment-related menopause (P = .0031).
Of women who reported that they did not want a future biologic child or were unsure (n = 309), 36% (n = 111) thought a future pregnancy would increase the risk of breast cancer recurrence, 48% (n = 148) did not think it would, and 16% (n = 50) were unsure. Of the women who felt a future pregnancy would increase their risk (n = 111), 20% (n = 22) reported greater concern about infertility at diagnosis compared with 80% (n = 89) who were less concerned.
The risk of infertility and menopause after treatment is a major issue for many young women with breast cancer. Previous research reveals that infertile women in the general population often report feelings of loss of control, depression, and low self-esteem, and women are generally more adversely affected psychologically by infertility than men.27,28 There is only limited information available about fertility concerns in women who have been diagnosed with breast cancer. Concerns about fertility may contribute to the greater psychosocial distress that younger women experience with the diagnosis and treatment of breast cancer.16-20 The potential for infertility may impact on a woman’s self-esteem and self-concept as a sexual person.20 Small qualitative studies have revealed that loss of choice about having children is a key concern both common and unique to young women with breast cancer,29 and that the possibility of becoming pregnant subsequent to breast cancer is a powerful stimulus for young women to get well.30 There is also evidence that the informational needs and concerns of women with breast cancer about fertility issues may change over time, with increasing concern and need for information further from diagnosis.31 The present study confirms the clinical experience that suggests that desire for children is an important factor in predicting greater concern about fertility and whether fertility issues will impact on treatment decisions. Some physicians may use the age of the patient and the stage of disease to prompt the discussion about fertility issues, assuming that younger women and women with lower-risk disease are more likely to be worried about treatment-related amenorrhea and the possibility of future infertility. However, our findings indicate that concerns about fertility are present for the majority of young premenopausal women, regardless of their age and extent of disease. Many younger women are also concerned about entering menopause with treatment, independent of their fertility. Problems related to premature ovarian failure include menopausal symptoms such as hot flashes, genitourinary problems, psychologic and psychosexual difficulties, and accelerated bone mineral density loss.21,32-38 Premature menopause may also contribute to increased cardiovascular morbidity, although data to support this in women with breast cancer are lacking. For many of these symptoms or complications, there are nonhormonal interventions available.39 Our findings suggest that a substantial proportion of women overestimate their risk of becoming postmenopausal with breast cancer therapy. This misperception is particularly worrisome in light of the fact that nearly one third of respondents indicated that fertility concerns impacted on their treatment decisions. Although therapy-related menopause is a consequence of adjuvant chemotherapy, the risk of premature menopause is related to patient age, the specific chemotherapeutic agents used, and the total dose administered.40,41 In women younger than 30 years, premature ovarian failure with standard regimens is quite uncommon, although available studies are generally limited by the small number of women evaluated in this particular age group. With standard anthracycline-based adjuvant chemotherapy including four cycles of doxorubicin and cytoxan, at least two studies have found a 0% incidence in this age group, with risks of premature ovarian failure that increase to the 10% to 15% range when considering women younger than 40 years of age.42-45 Rates in younger women after six cycles of cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil are somewhat higher; up to 20% of women 30 years of age and younger and up to 40% of women 40 years of age and younger will experience premature menopause.40,42-45 The impact of treatment duration and dose density, as well as newer drugs (eg, the taxanes), remains uncertain.46 Our study also reveals that some women may have been concerned about the impact of a subsequent pregnancy on breast cancer prognosis. Given available data, clinicians can try to correct inaccurate risk perceptions and educate young women about what is known and not known about risks of infertility and the potential impact of a future pregnancy on breast cancer prognosis. The present study suggests that there may be a need for improved communication about fertility between young women with breast cancer and their health care providers. Clinicians can share information on risk of infertility and premature menopause and discuss currently available options to preserve fertility, acknowledging the limitations of the data. Young women should be made aware of the conflicting evidence that chemotherapy-related amenorrhea may have a beneficial effect on breast cancer prognosis, of the benefits of ovarian suppression in those who do not receive chemotherapy,47-51 and of the availability of clinical trials currently being conducted to answer many of the issues that remain unclear. Finally, the lack of definitive data about the effects of a subsequent pregnancy on breast cancer prognosis remains problematic for many women.7,9,10,12,52-55 Our study is the largest research effort published to date addressing fertility concerns among young women with breast cancer. The sample size allowed us to evaluate a range of factors associated with fertility concern and allowed us to better understand the feelings of substantial numbers of women in all young age groups. However, this study has a number of limitations. Selection, nonresponder, and recall bias should be considered in evaluating the results. In particular, the women surveyed in this study were highly educated and motivated, and the feelings of members of a Web-based advocacy group may not reflect fully the sentiments or understanding of these issues among all young women with breast cancer. For example, women who join such a group are likely more educated and may be more concerned about infertility. Women in this group may also be more likely than the average young patient to have their concerns addressed, and yet a substantial proportion of women in this group did not feel fertility concerns had been addressed adequately. Many variables were evaluated, and the P values presented in the tables have not been adjusted for multiple comparisons. Thus findings of borderline statistical significance should be interpreted with caution. Finally, this was a cross-sectional retrospective survey of breast cancer survivors, and it is possible that perceptions of concern at diagnosis may change over time. Furthermore, use of psychometric measures such as the HADS and Lasry Fear of Recurrence Scale retrospectively may be limited by memory recall and distortions based on subsequent events.56 In conclusion, fertility remains a major issue for many young breast cancer survivors, and efforts should be made to elicit and adequately address fertility concerns at the time of diagnosis and treatment planning. Ongoing and future studies will help delineate the potential trade-offs between therapy-related menopause, future fertility, and breast cancer prognosis. In the meantime, increased attention to fertility issues at diagnosis and in follow-up may improve patient-provider communication and the quality of care received by young women with breast cancer. Clinicians and researchers should consider interventions, both psychosocial and medical, to diminish the impact of infertility on young breast cancer survivors.
The authors indicated no potential conflicts of interest.
We thank the members of the YSC for making this work possible.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
40 years at diagnosis of early-stage breast cancer who were concerned about the possibility of becoming infertile after treatment, to determine the percentage of women for whom fertility concerns impacted on treatment decision making, and to compare women who desired to preserve their fertility with those who did not with regard to fear of recurrence and relevant sociodemographic, clinical, and psychologic variables. 
