乌鸦传媒

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This installment: A noteworthy case study.

What's next for a premenopausal 40-year-old woman in Syria with recurrent hormone receptor-positive breast cancer in a setting with limited access to targeted therapies or genetic testing? That's what Maher Saifo, MD, of Damascus University in Syrian Arab Republic, and colleagues aimed to determine.

As the team explained in the , when the patient had been treated in Sept. 2005 at Albairouni University Hospital, she had undergone a right partial mastectomy with axillary dissection. Pathology findings then included grade 1 invasive ductal carcinoma (IDC), negative hormone receptors, and a HER-2 score of 2+.

The patient was married. Menarche occurred at age 13, and she had given birth to three children. Regarding her family medical history, her father died of lung cancer, and she had a niece with breast cancer.

The patient was started on adjuvant chemotherapy of six cycles of fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by radiation therapy. The response was good, and she was adherent to clinical and radiological follow-up, Saifo and co-authors said.

In Aug. 2009, the patient reported that her right breast had become smaller in size, with hardening behind the areola and nipple retraction. On clinical examination, the team noted a small lump in her right breast and enlargement of her right axillary lymph nodes. A biopsy of the mass identified IDC.

Four months later, in Nov. 2009, the patient started neoadjuvant chemotherapy with one cycle of FAC and two cycles of fluorouracil and cyclophosphamide -- the cumulative dose of doxorubicin was 630 mg (370 mg/m²). She underwent a modified radical mastectomy with axillary dissection.

Pathology examination identified grade 2 IDC showing a focal tubular pattern and the presence of metastatic carcinoma in two of 14 axillary lymph nodes. Hormone receptors were negative, HER-2 was 2+, and the tumor-nodes-metastasis stage was ypT1, N1, M0.

Subsequently, the patient received six cycles of adjuvant chemotherapy with paclitaxel and carboplatin. She developed grade 1 neutropenia, and anemia, but these adverse events were sufficiently mild that there was no need to adjust the dose, the case authors said.

CT scan of the patient's chest and abdomen, and a bone scan did not show any signs of additional metastasis; she received clinical and radiological follow-up.

Two years later, in Nov. 2011, clinicians ordered an ultrasound based on clinical suspicion of further metastasis. This revealed a 3.3×1.5 mm nodule located just above the collarbone. The lump was excised for analysis, and the biopsy revealed IDC.

Immunohistochemical analysis identified expression of progesterone receptor (70%) and estrogen receptor (10%), and an equivocal HER-2 score of 2+. The team recommended further chemotherapy with six cycles of paclitaxel followed by endocrine therapy (ET) with tamoxifen.

In Oct. 2012, follow-up chest x-ray and CT revealed "bilateral pleural effusion with two nodules in the upper and lower lobes of the right lung." Clinicians made a diagnosis of metastatic breast cancer, based on the patient's breathlessness, pleural effusion, and cytology findings. She received chemotherapy with carboplatin and intravenous vinorelbine.

In Jan. 2013, she developed chemotherapy-induced cardiomyopathy with a reduced ejection fraction of 45%, and had to be hospitalized. This occurred at a cumulative dose of doxorubicin of less than 400 mg/m², the authors noted. They said previous studies have put the incidence of heart failure in such cases at 3-5%, and 18-48% at a dose of 700 mg/m². This emphasizes the importance of regularly monitoring heart function after doxorubicin treatment, especially in patients receiving radiation therapy to the left chest wall.

The team discontinued carboplatin and started the patient on capecitabine with oral vinorelbine, and she was maintained on that regimen for the remainder of the year.

In Jan. 2014, she was scheduled for ET with an aromatase inhibitor (AI) -- anastrozole or letrozole, as available -- concomitantly with periodic zoledronic acid treatment. She received clinical examinations every 3 months, and chest x-ray, abdominal/pelvic ultrasound, laboratory tests, and tumor biomarkers every 6 months, as well as CT and bone scans as needed, and had a complete response.

Seven years later, in 2021, she developed osteoporosis. Clinicians replaced the AI treatment with tamoxifen, which they noted has bone-protective effects in postmenopausal women.

The patient also reported symptoms of paroxysmal nocturnal dyspnea. Chest x-ray showed interstitial pulmonary edema related to heart failure – her ejection fraction at that point was 33% -- and she received treatment with a cardiologist.

In Oct. 2023, PET-CT demonstrated complete response to ET, and the patient continued to respond and was doing well, the case authors stated. "Since the patient will have completed 10 years of ET, her case will be presented to a multidisciplinary team at Albairouni University Hospital to discuss stopping treatment and keeping the patient on close follow-up."

"Endocrine therapy achieved a complete and long-lasting response in this patient's metastatic breast cancer with malignant pleural effusion," the authors concluded. They noted that the currently first-line treatment for HR-positive/HER2-negative metastatic breast cancer – ET in combination with a cyclin 4/6-dependent kinase inhibitor (CDKI) -- has a reported progression-free survival time of approximately 25 months.

"According to recent recommendations, our patient should have been treated with AIs and CDKIs, but CDKIs were not available, so she was treated with AIs alone," Saifo and co-authors explained. "She survived for about 135 months and is still alive."

Discussion

This case demonstrates "the validity of endocrine therapy in recurrent hormone receptor-positive breast cancer, especially in countries that cannot afford targeted therapies or genetic tests," the team said.

Breast cancer is the second leading cause of malignant pleural effusion after lung cancer. The condition affects about 7-11% of all breast cancer patients, and is noted for rapid progression and a poor prognosis, with a median overall survival of 3-12 months.

The case authors pointed to updated results from the phase III of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Compared with letrozole alone, the addition of ribociclib improved the overall response rate from 29% to 43%.

Discrepancies in the results of hormone receptors and HER2 between the primary tumor and recurrence in this case, and in previous highlight the importance of performing tissue biopsies to confirm the status of molecular markers when there is a recurrence, the team noted.

One of the limitations of this case was that fluorescence in-situ hybridization was not available for diagnosis, which meant the patient was considered HER2-negative, suggesting "there is no difference in prognosis according to the in-situ hybridization status in HER2 2+ cases," the authors said.

The case confirms that endocrine therapy remains the cornerstone of treatment for metastatic breast cancer, especially in the absence of targeted agents, and demonstrates the challenges facing low-resource countries in cancer management, Saifo and colleagues concluded.

Read additional installments in this series here.