SCINTIGRAPHIC PATTERN OF SKELETAL METASTASIS BASED ON MOLECULAR SUBTYPES OF BREAST CANCER AT THE DR GEORGE MUKHARI ACADEMIC HOSPITAL GARANKUWA, SOUTH AFRICA

Introduction: The presence of metastasis is the most important factor affecting overall survival of patients with breast cancer. Though tremendous progress has been made in area of treatment, 20-30% of patients will develop metastasis, with the skeleton as one of the major sites of distant spread. There is marked variability among breast cancer patients who develop metastasis including the pattern. The histopathological molecular subtypes of breast cancer have distinct biological features with variability in the metastatic pattern, response to treatment and overall clinical outcome. Bone scintigraphy (bone scan) is the most commonly used imaging modality for the detection of skeletal metastasis and Methylene diphosphonate (MDP) complexed with gamma-emitting radionuclide technetium-99m (99mTc-MDP) is the most commonly used tracer for this imaging.

Objective: To assess the pattern of occurrence and distribution of skeletal metastases detected by 99mTc-MDP bone scintigraphy in the various molecular subtypes of breast cancer at the Dr George Mukhari Academic Hospital Garankuwa, Guateng.

Methods: A retrospective review of all the bone scans of two hundred and two consecutive breast cancer patients irrespective of their clinical details (age, menopausal status, stage, treatment received, presence of other metastatic sites etc.) seen at the Department of Nuclear Medicine of Dr George Mukhari Academic Hospital, Garankuwa South Africa, between 2011 to 2015 was conducted. The patients were classified into four molecular subtypes (Luminal A, Luminal B, Human epidermal growth factor receptor-2 enriched (HER2-enriched) and Triple-negative) based on the expression of estrogen receptor (ER), progesterone receptor (PgR), Human Epidermal Growth Factor Receptor-2 (HER-2) and Ki-67 determined by immunohistochemistry at the time of diagnosis. All the patients had a minimum of two annual bone scans done between 2011 and 2015. The bone scans were reviewed for the presence of skeletal metastases and those with skeletal metastases were further classified into respective histopathologic molecular subtypes. Relevant data related to demographic information, clinical presentation, metastasis pattern, and histopathological details of the patients were retrieved from the case folders and entered into a proforma.

Results: A total of 202 patients met the study eligibility criteria; out of which 106 (52.5%) had skeletal metastasis (positive bone scans). The mean age at presentation of patients was 57.9 years with 77.4% at stages 3 and 4. The majority (72%) of the patients were ER-positive, about (46.2%) were of the Luminal B molecular subtype while Luminal A, triple-negative, and HER2-enriched subtypes accounted for 27.4%, 17% and 9.4% respectively. The highest frequency (77%) of occurrence of bone metastasis was seen in the HER2-enriched subtype. The multiple metastasis pattern of metastasis were the commonest (77.4%) pattern of distribution noted followed by solitary pattern, while super scan pattern was the least common (2.8%). Thoracolumbar vertebrae were the most commonly affected site while bones of the lower extremities had the least affectation. The sternum was the most common site of affectation noted with the solitary pattern of distribution. The multiple metastases pattern of distribution remained the most frequent in all molecular subtypes, the solitary was noted more (71.4%) with the luminal subtypes while super scan was found only in the luminal subtypes.

Conclusion: This study has shown that multiple metastasis pattern of distribution of skeletal lesions remains the most frequent form with the thoracolumbar vertebrae and lower extremities being the most and least affected sites respectively. The solitary and super scan patterns are commonly associated with the luminal subtypes. The findings could guide the development of surveillance protocol to predict bone metastases in breast cancer patients based on molecular subtypes.