The patient, a 49-year-old premenopausal woman, was admitted to the emergency department in August 2013 with persistent, severe, cramping back pain, but otherwise in good health. Her symptoms began in May 2013, when she felt as if her “rib broke” during a sneeze, and in June 2013, she had a normal chest X-ray. She was put on cyclobenzaprine, naproxen, and physical therapy, but after a long flight in July 2013, she felt as if she “threw out her back” while getting up. The back pain was now only manageable with narcotics and was accompanied by urinary and fecal urgencies. On workup at the emergency department, a chest X-ray was notable for a new thoracic vertebral compression fracture not seen two months prior. A follow-up computational tomography (CT) imaging revealed diffuse lytic lesions throughout the lumbar spine, sacrum, and ilium, which were read as concerning for metastases or myeloma with no evidence of intrathoracic, intra-abdominal, or intrapelvic malignancy.

In light of possible metastases, the patient was admitted to the oncology service. Physical examination revealed slight retraction of the right nipple, with subjective increased density of the right breast tissue as compared to the left breast; otherwise, the examination was within normal limits. Serum laboratory tests showed elevated calcium (11.6 mg/dL), albumin (4.0 g/dL), and a mildly elevated alkaline phosphatase (136 mg/dL). Magnetic resonance imaging (MRI) of the thoracic and lumbar spine revealed tumor within the eleventh thoracic (T11) vertebral body, leading to moderate spinal canal stenosis, with epidural enhancement extending from the inferior tenth thoracic level to the superior twelfth thoracic (T12) level and neoplastic extension anteriorly immediately adjacent to the posterior aorta. Diffuse tumor was identified in all lumbar vertebrae, multiple adjoining ribs, and iliac bones. Follow-up mammography revealed a “highly suspicious” sonographic and mammographic abnormality of up to 6 cm at 9:00 in the right upper-outer breast, composed of fine pleomorphic calcifications, scoring 5 on the Breast Imaging Reporting and Data System scale.

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The breast was explored as the potential primary site of the cancer. Right breast core biopsy at 9:00 showed a moderately differentiated invasive ductal carcinoma (IDC) that was estrogen receptor positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor 2 negative (HER2−), with a Ki67 score of 25% (Table 1A), consistent with stage IV breast cancer. No germline mutations were identified. CT-guided core biopsy of the right iliac bone revealed metastatic IDC that was ER+, PR−, and HER2−, with a Ki67 score of 10% (Table 1A). Representative images of the IDC in both the right breast and right hip are shown in Figure 1A and B. The patient underwent a laparoscopic bilateral salpingo-oophorectomy, which was histologically unremarkable.

(To view a larger version of Figure 1, click here.)

(To view a larger version of Table 1A, click here.)

In September 2013, she was enrolled in a phase III trial of letrozole, an aromatase inhibitor, and palbociclib, a cyclin-dependent kinase 4/6 inhibitor, versus letrozole and placebo. She received infusion regularly to manage hypercalcemia. In November 2013, she began to notice weight loss and decreased appetite, for which she was referred to nutrition services. She continued through 19 cycles of chemotherapy, with 95–100% compliance to the therapeutic regimen, before exiting the study in the middle of her 20th cycle in late March 2015, in view of disease progression. She was unblinded and determined to be receiving palbociclib and not placebo. The breast mass size over the course of chemotherapy is presented in Table 1B.

(To view a larger version of Table 1B, click here.)