Breast cancer treatment and timing for fertility preservation

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. 

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James Fleck, MD, PhD: Full Professor of Clinical Oncology at the Federal University of Rio Grande do Sul, RS, Brazil 2022