Around 6% of women diagnosed with breast cancer are under the age of 40. Younger or premenopausal survivors report lower QOL, greater severity of depressive symptoms, and higher levels of stress compared to older survivors.39,40 Often younger women have not begun or completed their childbearing at the time of diagnosis. As a consequence, fertility preservation becomes a primary concern for younger breast cancer patients. Infertility caused by cancer treatment is a source of significant psychosocial distress and decreased QOL.39-41
The American Society of Clinical Oncology (ASCO) recommends health care providers refer patients within their reproductive years for fertility counseling.41 While the proportion of patients who do not remember any discussion regarding fertility has been gradually decreasing over time, up to 50% of patients still have no memory of a conversation about fertility at time of treatment planning.42-47
Issues surrounding the timing of fertility counseling are complex. Some fertility planning techniques such as embryo or oocyte cryopreservation require 2 weeks from the beginning of a menstrual cycle. If a patient chooses this option, cancer treatment may be delayed a month or more. Additionally, a patient may require some time to contemplate her fertility options before making a decision. Conversely, additional psychological stress may be added unnecessarily if a patient has a premature referral to reproductive counseling in a case where chemotherapy is not indicated. Specialized counseling regarding fertility has been associated with both an increased QOL and less regret, regardless of whether action is taken to preserve fertility.48,49 Counseling should include descriptions of the available techniques, success and failure rates, complications, and whether a procedure is experimental or not.
Although up to 45% of women express a desire for a future child at the time of diagnosis, only 3% to 8% go on to have a full-term pregnancy after cancer treatment.39,47,50,51 Ovarian reserve, or the capacity of the ovary to provide eggs capable of fertilization, decreases naturally as women age. Despite some women experiencing resolution of their treatment-associated amenorrhea, patients should be counseled that their reproductive potential may be impaired even in the presence of regular menses.52,53
The choices for fertility preservation vary depending on the patient’s age, planned cancer treatment, partner status, ovarian reserve, time frame available, and the possibility the cancer has metastasized to the ovaries.52 The main options for fertility preservation include embryo cryopreservation, oocyte cryopreservation, and temporary ovarian suppression (Table 83-2). Cryopreservation of ovarian tissue or of immature oocytes is still experimental. The data regarding efficacy of temporary ovarian suppression with luteinizing hormone-releasing hormone analogue (LHRHa) is conflicting.54-59 Both oocyte and embryo cryopreservation require 10 to 14 days of ovarian stimulation and are expensive. They may be offered when it is reasonable to delay treatment by 2 to 6 weeks and the patient is below the age of 38 to 40 with the possibility to recover an adequate number of oocytes.52 Concern remains regarding the impact of the ovarian stimulation required for embryo or oocyte cryopreservation upon hormone-sensitive tumors. Further research in this area is required.
Fertility Preservation Options in Women Diagnosed with Breast Cancer
|Favorite Table|Download (.pdf) TABLE 83-2
Fertility Preservation Options in Women Diagnosed with Breast Cancer
|Fertility Preservation Options for Breast Cancer Patients |
| ||Requirements ||Effectiveness ||Estimated Cost |
|Embryo cryopreservation || ||20–30% of transfers result in live births || |
|Oocyte cryopreservation ||10–14 days of ovarian stimulation || || |
|Temporary ovarian suppression ||Use of luteinizing hormone-releasing hormone analogue || ||N/A |
|Cryopreservation of immature oocytes or ovarian tissue ||Currently require enrollment in research protocols ||Experimental ||N/A |
The incidence of treatment-related ovarian failure in breast cancer patients depends mainly on patient age, use of tamoxifen, and the type of chemotherapy used. Alkylating agents appear to have the greatest risk, although carboplatin and cisplatin may also have deleterious effect upon ovarian function.60,61 Data demonstrating a link between amenorrhea and taxanes remains inconclusive.52,62 Tamoxifen alone is associated with a low risk of premature menopause which is related to increasing age.52 However, adding tamoxifen to a chemotherapy treatment regimen significantly increases both the rate of amenorrhea and the risk of infertility.60,63
Patients often have mixed feelings about pregnancy after breast cancer. For many women, pregnancy can represent a return to normalcy and be associated with happiness and fulfillment. Women or their partners may fear congenital abnormalities, a risk of cancer recurrence, and guilt about having a child when they might die or be ill. The rate of congenital abnormalities of infants born to women with a previous diagnosis of breast cancer is similar to that of the general public (0% to 7.2% vs. 4%).64-69 In a large multinational study reviewing breast cancer diagnosed during pregnancy, chemotherapy was administered to 200 patients during their pregnancy with no negative effects noted on the fetus when given in the second and third trimester.70 No increase in congenital abnormalities was seen; however, an increase in early delivery was reported.70 Regardless, breast cancer survivors who become pregnant should be referred to a high-risk obstetrician for close monitoring.
The impact of pregnancy on breast cancer disease-free survival rates has been a focus of increased research. A large multinational study noted no observed differences in either disease-free survival or overall survival based on pregnancy at time of breast cancer diagnosis.70 A meta-analysis suggested a lower risk of breast cancer recurrence in patients who had a pregnancy after breast cancer, but there were concerns for selection bias, as patients who choose to become pregnant usually do not have recurrence.71 In an attempt to eliminate possible bias from earlier studies, a multicenter retrospective cohort study was performed comparing disease-free survival in patients both with and without a subsequent pregnancy matched for estrogen receptor status, age, nodal status, and adjuvant therapy.72 Three hundred and thirty-three patients with a pregnancy were matched to 874 patients without a pregnancy. No adverse effect on disease-free survival was noted in the patients who became pregnant after breast cancer. This suggests pregnancy after a diagnosis of cancer may be considered safe.72
The ideal interval between conception and cessation of treatment is undecided. Most cancer specialists recommend waiting 2 years to allow manifestation of early recurrence before becoming pregnant.73 A large prospective cohort study performed by the Breast International Group and North American Breast Cancer Group (BIG-NABCG) aims to evaluate patient and offspring outcomes including disease-free survival, overall survival, abortion, miscarriage, still-birth rates, live-birth rates, and birth defects.74 The study is divided into two phases: (i) to investigate the feasibility and impact of temporary treatment interruption for conception at 18 months versus 36 months of treatment and (ii) the optimal duration of endocrine treatment after delivery or last failed attempt to get pregnant.74
There is scant data on the subgroup of patients who are BRCA1 or BRCA2 positive and desire pregnancy. BRCA1 patients tend to have a hormonal nonresponsive tumor.75 An international multicenter cohort study of BRCA1 or BRCA2 subjects who were diagnosed while pregnant or became pregnant after a diagnosis of breast cancer and were matched with BRCA-positive patients who did not become pregnant found that pregnancy concurrent with or after a diagnosis of breast cancer did not appear to adversely affect survival.76
Finally, lactation is possible following unilateral mastectomy, and an adequate supply of milk may be provided by the surviving breast.77 In the affected breast, lactation issues can occur after breast-conservation surgery and radiotherapy.78,79 There may be minimal or no enlargement of the affected breast during pregnancy, and milk supply may be decreased or absent.78,79