|Year : 2020 | Volume
| Issue : 1 | Page : 37-41
Fertility preservation in breast cancer
Sadhana Patwardhan, Mangala Ketkar, Rita Bang, Nitya Agrawal
Nagpur Test Tube Baby Centre and Ketkar Hospital, Nagpur, Maharashtra, India
|Date of Submission||28-Nov-2019|
|Date of Acceptance||07-Jul-2020|
|Date of Web Publication||30-Jan-2021|
Dr. Sadhana Patwardhan
Nagpur Test Tube Baby Centre and Ketkar Hospital, Madhav Nagar, Nagpur - 440 022, Maharashtra
Source of Support: None, Conflict of Interest: None
Fertility preservation is a discipline that has emerged within the past 20 years and aims to enhance the quality of life of survivors by preserving their reproductive endocrine capacity. The need for fertility preservation has to be weighed against morbidity and mortality associated with cancer. There is thus a need for a multidisciplinary collaboration between oncologists and reproductive specialists to improve the awareness and availability. Increasing the lifespan of cancer survivors due to early diagnosis and management and current trend of delaying childbearing has led to many cancer survivors who intend to have a child after cancer treatment, hence comes the role of oncofertility. Herein, we report a case of cancer breast who underwent in vitro fertilization at our center for fertility preservation.
Keywords: Cancer, fertility preservation, oncofertility, reproductive capacity
|How to cite this article:|
Patwardhan S, Ketkar M, Bang R, Agrawal N. Fertility preservation in breast cancer. Onco Fertil J 2020;3:37-41
| Introduction|| |
Breast cancer is the most common cancer among women. Seven percent of women<40 years and 11%<45 years suffer from it and more than 50% live for 20 years or more. In accordance with an ongoing rise in its incidence among young women, with the current social trend to delay motherhood until later in life, we nowadays witness an increasing the number of patients who have not completed childbearing when cancer is diagnosed and are likely to desire pregnancy once cure has been confirmed.,
Why fertility preservation is necessary for women with breast cancer management
Surgical therapy, i.e., mastectomy causes lot of stress and psychological morbidity and impairs fertility through hypothalamic-pituitary-gonadal axis dysfunction which causes anovulation and amenorrhea. The chemotherapy and/or radiotherapy employed the results in follicular damage with either low ovarian reserve or premature ovarian insufficiency.
Counseling of the patient and both the partners if married is to be undertaken by a multidisciplinary team consisting of surgical, medical, and radiation oncologist along with fertility specialist. The main issues to be discussed are the survival rate after therapy for cancer, recurrence rates, importance of compliance to therapy, effects of chemotherapy, and radiotherapy on ovarian function and the options for preserving fertility such as oocyte cryopreservation, embryo cryopreservation, and ovarian cortex cryopreservation along with the success rates of assisted reproductive technology (ART). The complications of drug used for controlled ovarian stimulation (COS) such as ovarian hyperstimulation syndrome and its effect on the breast cancer should be explained. The patient should also be counseled about her ovarian reserve, which will affect the number of oocytes retrieved. The outcome of ART which includes the fertilization rate, cleavage rate, and blastulation rate along with the success of vitrification of cleavage stage embryos or blastocyst needs to be explained.,
Timing of embryo transfer after cure of cancer and the fear of congenital malformations, recurrence of cancer, and myths of transmission of breast cancer to the offspring are to be wiped off. Counseling to test for BRCA gene status is also important.
[Table 1] below gives the 5 years' survival rate for breast cancer.
| Case Report|| |
A 30-year-old female married for 9 months had a lump in the left breast for 2 years which was diagnosed to be benign on the clinical examination. In December 2018, she had a painful swelling in the left axilla, which was diagnosed on biopsy to be infiltrative ductal carcinoma, Grade III. She underwent a modified radical mastectomy on 4/4/19. On immunohistochemistry, the lesion was found to be estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor II receptor positive. The pathological stage (tumor, node, and metastasis) was T2N1M0. The grade of invasive ductal carcinoma was grade III. BRCA gene status done was negative. Postoperative both chemotherapy and radiotherapy was required, so was referred for fertility preservation to Nagpur Test Tube Baby Center.
Her last menstrual period was on March 30, 2019 (The patient came on 20/04/19 that is day 22 of her menstrual cycle (MC) for an opinion on fertility preservation). The cycles were regular. Her sister also was diagnosed with fibroadenoma. On sonography, she had 3 antral follicles on each side and a good endometrium. Her antimullerian hormone level was 0.92 ng/ml. Husband had normal sperm count and motility. The patient underwent a conventional follicular start Antagonist protocol. Tablet Letrozole 5 mg was started from Day 2 of her MC. She also received gonadotropins in the form of recombinant follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from day 2 of her MC. Agonist trigger was given when follicular diameter of the dominant follicle was 18 mm. Five embryos were formed and frozen. Letrozole was continued in the luteal phase to reduce the estrogen levels. She received six cycles of chemotherapy (TCH regimen-Taxotere/Docetaxel, carboplatin, and herceptin). She is planned for 3 weeks radiotherapy and weekly injections of herceptin for a year. After the complete remission of disease, the patient will planned for frozen embryo transfer.
| Discussion|| |
The safety and concerns of stimulation for fertility preservation in breast cancer patients.
For peak eastradiol levels
Conventional ovarian stimulation may have deleterious effect on tumor progression, especially in hormone-positive tumors because of the high estradiol levels. Letrozole in the dose of 5 mg is added from day 2 or 3 of the cycle along with the gonadotropins till ovulation trigger to reduce the peak estradiol levels. After oocyte retrieval, letrozole is again continued further till the next MC.
By comparing the use of GnRH agonists versus HCG trigger for oocyte maturation, it was found that the agonists achieved a greater and faster decline of the estradiol levels without reducing the number of mature oocytes collected or the fertilization rate.
COS protocols sometimes incorporate tamoxifen in a GnRH-antagonist cycle for the protection against high estradiol levels during stimulation.
For time delay
When a cancer patient is referred for fertility preservation, the oncology team dictates the time available for her ovarian stimulation, depending on when the chemotherapy needs to be started. Random start stimulation protocols have been specifically designed to avoid the delay in starting chemotherapy after in vitro fertilization (IVF) cycle is completed: Following are the different stimulation protocols used in women for fertility preservation
- Conventional (early follicular phase) start: Stimulation starts with menses and antagonist is added to prevent premature LH surge once the lead follicle reaches 12 mm
- Late follicular phase start: Start FSH or hMG if leading follicle<12 mm. Add GnRH antagonist when leading follicle >14 mm, pituitary suppression with GnRH antagonist for 4–7 days followed by gonadotropins. GnRh antagonist restarted again once the dominant follicle is more than 14 mm. Induce ovulation with GnRH agonist if follicle >16 mm. After ovulation start with the luteal phase protocol
- Luteal phase start: The patient would have already ovulated or if has a dominant follicle more than 14 mm induce ovulation with either hCG or GnRH agonist. COS started within 2–3 days in the luteal phase. GnRH antagonist administration is initiated when the follicle cohort reached 13–14 mm to prevent premature secondary LH surge. Either a hCG or GnRHa is given for trigger
- Luteal halt: The administration of GnRH antagonist in the luteal phase induces corpus luteum regression. Menses usually ensues 2–4 days later after which COS started. The advantage is that ovarian stimulation is initiated earlier than spontaneous menses.
Breastfeeding after breast cancer
There is no evidence that breastfeeding increases the risk of breast cancer recurrence. Breast feeding after breast cancer treatment is not contraindicated for women who do not show any evidence of residual tumor and should be supported with adequate information and counselling. Breast cancer treatment may impair the capability of nursing because of the reduction of milk production related to surgery and radiotherapy.,
Optimal timing of pregnancy after the conclusion of cancer treatment
Optimal timing of pregnancy after the conclusion of cancer treatment is uncertain and depends on patient-specific factors (type of treatment, tumor type, and prognosis). Moreover, recurrence pattern vary according to the molecular subtype of breast cancer and highest risk for cancer recurrence is in the first 2 years after completing treatment. Therefore, it is best to wait for this time period before attempting conception.,,
Patients negative for ER tend to have relapse within the first 2 or 3 years after the diagnosis and treatment. However, luminal type of disease is prone to late relapses, sometimes, even after 5 years. In hormone-positive breast cancer patients, women should be fully informed about the risk of stopping tamoxifen prematurely. It is recommended to complete endocrine therapy after pregnancy if it occurs. Experts recommend waiting for at least 4–6 months from the end of chemotherapy and the attempt to conceive. The interval recommended after the end of hormone treatment is at least 3 months. Pregnancy should be planned only after a thorough evaluation and confirming cancer remission or cure. During primary cancer treatment and till pregnancy is planned, it is recommended that safe, nonhormonal contraception should be used. However, a pregnancy that occurs spontaneously within the first 2 years after completing cancer treatment does not suggest that cancer is more likely to recur.
Risk of miscarriage, preterm birth, growth restriction, and stillbirth
Risk of miscarriage, preterm birth, growth restriction, and still birth depends on the type of therapy received (chemotherapy, radiation therapy, and surgery) and on non-treatment factors (such as age at start of pregnancy, type, and site of neoplasm). It has been noted that there is increased risk of adverse pregnancy outcome among female cancer survivors. Chemotherapy does not appear to damage the uterus, which may account for favorable pregnancy outcome in exposed patients but had lower rate of live birth rate compared to siblings. Exposure of the uterus to high doses of radiation can disrupt endometrial receptivity and pregnancy maintenance and may lead to preterm birth, fetal growth restriction, and still-birth.,
Risk of congenital and chromosomal abnormalities in the children born after the treatment of breast cancer
Children born from mothers who have received chemotherapy are not at higher risk for congenital defects compared with the general population. Children of women treated for breast cancer carry an increased risk of cancer only in the presence of BRCA mutation. Preimplantation genetic diagnosis (PGD) can identify embryos without the BRCA defect, thus allowing to select BRCA-negative embryos for embryo transfer.
Effect of pregnancy on survival outcomes
Most studies have shown benefit or no effect of pregnancy on survival outcomes.,,,
Parity and number of children appear to be protective against developing breast cancer in the carriers of BRCA1 and BRCA2 mutation.,,, Women with BRCA1 and BRCA2 mutations did not find an adverse effect of fertility treatment on the risk for developing breast cancer, compared with controls (odds ratio, 1.21; 95% confidence interval, 0.81–1.82)..
BRCA mutation carriers
Approximately 10% of breast cancer cases are because of germ-line mutations in susceptibility genes, especially BRCA 1 and BRCA 2. BRCA 1 mutation carriers are at a 50%–80% lifetime risk of breast cancer. These patients seem to present with lower ovarian reserve at baseline as compared with noncarriers, which would itself represent an obstacle to achieve pregnancy. BRCA mutation carriers who have already been diagnosed with cancer are more likely to present with triple-negative tumors, which generally have poorer prognosis than other breast cancers. Women with BRCA mutations, on the other hand, should be made aware of fertility issues and also motivated to consult fertility preservation specialists earlier. These women may also request PGT-M for BRCA mutations during IVF to prevent mutation transmission to the child.
Barriers to use fertility preservation
Barriers to use fertility preservation are the lack of patient awareness due to inadequate discussion of treatment-related fertility risks, expected burden of the FP process itself, significant financial burden associated with embryo/oocyte cryopreservation, and absence of insurance coverage. The other causes are health-related concerns such as fear of future cancer recurrence or treatment-related complications, anxiety about treatment delay, and fear about the safety of future pregnancy and children born from these preganncies.
| Conclusion|| |
In treating young breast cancer patients, it is important to assess fertility desire, discuss treatment risks relating to fertility and discuss fertility preservation options. While the patient tries to compartmentalize the ramifications of her disease, oncologists and fertility providers alike should emphasize that survival and fertility are not mutually exclusive. Pregnancy after breast cancer is possible and that it can be achieved safely for both mother and child. The patient can survive her cancer and have a family. Motherhood after cancer survival ushers in a new dawn.
Increasing awareness among health-care providers is needed to make such cancer survivors opt for fertility preservation services and improve their quality of life by rearing their own biological child.
Our patient underwent a successful IVF cycle for fertility preservation. She is planned for frozen embryo transfer after her radiotherapy once she is fit to conceive.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that their names and initials will not be published. Due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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