Take-home Message
How to deal with fertility preservation before starting curative treatment of a young patient with triple negative breast cancer. The use of a sequential approach.
(Fictional narrative by the doctor)
James Fleck: Anticancerweb 02 (02), 2022
Lyla's staging tests were normal. Immediately, she was referred for surgical breast evaluation and genetic counseling. Usually, breast-conserving surgery is recommended. The surgery consists of a lumpectomy, in which the tumor is completely removed, with an appropriate safety margin. During the surgical procedure, a radioactive material is injected into the tumor area and a probe is used to identify the first draining lymph node. Called a sentinel node, it is first examined by a pathologist using an intraoperative frozen section for metastatic tumor cells. If the sentinel node is negative, there is no need to increase lymph node sampling. If positive, an enlarged sampling of the ipsilateral axilla would be necessary to assess the number of affected lymph nodes. This information is essential for prognostic assessment and definition of the best recommendation for adjuvant systemic treatment. Breast-conserving surgery also requires adjuvant radiation therapy.
However, in Lyla's case, the decision making was not routine. She had strong genetic susceptibility as there was a family history of breast cancer and she had been diagnosed with breast cancer at a very early age. She would be evaluated for BRCA1 and BRCA2 mutation. The presence of a double mutation in the tumor suppressor genes would classify Lyla as having a very high risk of local recurrence, de novo contralateral breast cancer, ovarian cancer and Fallopian tube cancer. This would require preventive recommendations. The BRCA1 and BRCA2 mutation would challenge the best type of breast surgical approach, as well as the need for bilateral prophylactic salpingo-oophorectomy. Mutation in both suppressor genes would lead to an 85% lifetime risk of developing a new breast cancer. Additionally, the risk of ovarian cancer would progressively increase with age until reaching 50% in the population at risk.
Preventive recommendations can range from increased surveillance using breast MRI and routine gynecological check-ups to more radical surgical procedures. After clear discussion of the risks, most patients accept bilateral prophylactic mastectomy, followed by removal of both ovaries and Fallopian tubes. But, in Lyla's case, there was another aggravating factor. Tumor pathological and immunohistochemical exams revealed a basaloid type, which, regardless of the expression of BRCA1 and BRCA2 mutation, would result in a worse prognosis. This type may be associated with other genomic alterations not yet adequately studied and well identified by the international scientific community. Another central issue would be the timing of the procedures. Lyla would like to have a child and that would only be possible collecting eggs, which cryopreserved would later be used for assisted reproduction.
Lyla and her family consulted with some genetic counseling professionals. After understanding all the technical and ethical issues involved, they decided to go ahead, testing for the BRCA1 and BRCA2 mutation. At that time, gene sequencing evaluation required approximately ninety days to obtain a comprehensive and reliable result. I couldn't delay her cancer treatment that long. The biological expression of Lyla's tumor was very aggressive and her treatment should be started immediately. I met with Lyla and her family and proposed a sequential approach. Lyla would begin a routine treatment with lumpectomy, sentinel node assessment, and additional adjuvant treatments according to the pathologic findings.
They agreed and surgery was scheduled. At the same time, under the guidance of multi-professional genetic counseling, Lyla had started assisted reproduction procedures. She underwent a program to obtain oocytes, egg precursor cells. They would be obtained by puncturing the ovarian follicles and subjected to cryopreservation for future in vitro fertilization. It was a new technology with incipient results. Lyla was aware of the technical limitations and ethical implications. Even so, she remained adherent in her quest for motherhood. While I fully understood the patient's broader goals, my focus remained on treating her breast cancer.
On the day scheduled for the breast lumpectomy, I went to the operating theater. There I met with the surgeon, the anesthesiologist, the pathologist and an MRI doctor. Together, they would work on the intraoperative location of the tumor.
The procedure has started. Lyla had no problems with anesthetic induction. The surgeon, guided by previous MRI findings and technical support from the radiologist, accurately identified the anatomic location of the tumor. He performed a lumpectomy with a wide surgical margin. He injected radioactive material into the tumor bed to assess lymphatic drainage and identify the sentinel node. Using a probe, he located the sentinel node in the ipsilateral axilla, removing it for intraoperative pathological examination. The pathologist declared that the surgical margins of the primary tumor were safe and the microscopic examination of the sentinel lymph node was positive. This was an unfavorable finding that required further exploration of the axilla, seeking a larger sample of lymph nodes.
Lyla endured the postoperative period very well and was discharged on the third day. Her material was carefully evaluated in the pathology lab. The result confirmed the previous biopsy finding. It was a basaloid-type breast carcinoma, measuring 2.2 cm in diameter. The surgical margins were tumor free and the sentinel lymph node was positive. Evaluation of axillary sampling revealed the absence of histological involvement in the additional 23 dissected lymph nodes. There was no expression of estrogen, progesterone or Her-2 receptors, confirming its triple negative molecular classification. An evaluation by a more sophisticated technique called PCR showed micro metastatic disease in two of the 23 axillary lymph nodes examined.
Lyla had an aggressive disease, characterized by unfavorable histological and immunohistochemical expression, accompanied by metastases in axillary lymph nodes. There was also the possibility of expressing a germline mutation in the BRCA1 and BRCA2 tumor suppressor genes. Although the imaging tests did not show the presence of metastases in other organs, the unfavorable biological characteristics of this tumor pointed to a high probability of micrometastases. These clinically undetectable cells may have early migrated through the bloodstream, establishing themselves in target organs. This was just an assumption, based on the high recurrence rate observed in the first three years of follow-up in young patients with the same biological profile. My recommendation for treatment was dose-dense chemotherapy, where the drugs would be given every other week. It was a very toxic program, but it had been shown to lower the risk of relapse, further increasing the chance of cure. To minimize complications, Lyla would receive support to prevent her white blood cells from falling, using a protective drug called filgrastim.
To be continued in PLOT 4 (climax) …
* Attention: The story 9 will be published sequentially from PLOT 1 to PLOT 6 and you will always see the most recent posting. To read Story 9 from the beginning, just click in the numbered links located at the bottom of the homepage.
© Copyright Anticancerweb 2022
James Fleck, MD, PhD: Full Professor of Clinical Oncology at the Federal University of Rio Grande do Sul, RS, Brazil 2022
The preservation of fertility must be a basic right that must be guaranteed for women. It is known that, unfortunately, this is not yet worked out correctly with these patients. I think that we medical students, and especially women, need to fight for this right of our patients to be fulfilled in order to be. Therefore, it is important that we talk about this with our patients and demand that our colleagues also talk about it.
For some part of woman the wish of becoming a mother is a goal in life, and that include people with cancer. This right must be guaranteed and everything must be done to accomplishment that for oncologic patients. It is up to science to develop ways for these patients' fertility to be preserved and for health professionals to offer the best opportunities.
This kind of situation is pretty common among patients with gynecological cancers. One of the rights of a woman is to have the choice of having a child or not. For many of us, this is an important step of social and cultural acceptance and also a representation of fulfillment for those who had always dreamt about motherhood. In the case of this patient, it also existed a factor of guilt, which makes it more difficult to deal with in the process of treating her. Because of all of this, it is extremely important for all future doctors to always try to remember what fertility preservation means to a woman.
Breast cancer is among the most common cancers both affecting and killing women in the world. And like any other cancer, its treatment may cause infertility in women during their reproductive years. Therefore, assessing fertility preservation during breast cancer treatment should be a matter of greater awareness. Motherhood may represent for most women the achievement of a dream, a chief step into cultural acceptance, the right to grow a family of their own. Thus, the medical team must explain the risks concerning fertility when in need of cancer treatment and offer time, space, and comfort so that the patient can make up her mind about it and chose whether to preserve eggs or not.
Breast cancer conveys not only a medical significance, but also an emotional one during diagnosis and management. New technologies for the detection of markers that indicate the chances of a relapse are of extreme importance and value in nowadays Medicine. Considering the emotional side of it, as well as the patient as a whole, we should ponder and comprehend the angst that this information and also the procedures for cancer treatment can cause in a young woman that wishes to reproduce. It definitely is a sensitive subject and a comprehensive conversation between the medical team and the woman should happen considering her wishes and future perspectives.
The preservation of fertility is a question for women who are diagnosed with cancer and have a desire for motherhood. Treatment can have an impact on fertility, so it is essential that, before starting it, the oncologist shows the options to assure the woman the right to have a child, if that is her will.
When a woman discovers breast cancer, she deals with many thoughts and emotions. Treatment, even if effective, can lead to loss of fertility, which can be devastating for women who intend to have children. Therefore, it is extremely important that oncologists talk about options to ensure that this patient can have her dream of motherhood come true.
The desire to become a mother at some point in life should not be another aspect to be impacted along the path of cancer treatment. Therefore, it is very important that a dialogue takes place between doctor and patient about the possibility of preserving fertility in these patients who had always had this dream.
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