Swipe to advance
Images from Guimaraes MD, Bitencourt AG, Marchiori E, Chojniak R, Gross JL, Kundra V. Cancer Imaging. 2014;14:18. [Open access.] PMID: 25609051, PMCID: PMC4331823.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Death rates from breast cancer in the United States have decreased steadily in women since 1990,[1] thanks to earlier detection and improved treatment modalities. However, nearly 50,000 US female breast cancer-related deaths are still expected annually,[1] and this disease remains the leading cause of cancer death among women worldwide (an estimated 627,000 deaths in 2018).[2]

Metastatic breast cancer, also known as stage IV or advanced breast cancer, refers to spread of the disease via the lymph nodes or blood from beyond the breast to distant sites, such as the bones, lungs, liver, brain or skin.[3] This condition is incurable, and the 5-year survival for metastatic breast cancer is about 6%.[1]

The axial (A) and sagittal (B) postcontrast T1-weighted magnetic resonance images (MRIs) show breast cancer metastatic to the spine. A bone lesion in the posterior elements of T6 (arrowhead) has high T2 signal intensity and intense contrast enhancement; it is impressing on the spinal canal and displacing the cord anterolaterally (arrow).

Image from Subbiah V, Chuang HH, Gambhire D, Kairemo K. Diagnostics (Basel). 2017;7(1). [Open access.] PMID: 28212290, PMCID: PMC5373019.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

The images shown are pre- and post-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans in a middle-aged woman with metastatic breast cancer and multiple osseous metastases, at baseline (BL) and again at 6 weeks (wk), 4 months (mo), and 10 months after initiation of treatment. At 10 months, new focal sites of activity appeared but without anatomic abnormality. CT = computed tomography; MIP = maximum intensity projection.

Symptoms/signs of metastatic spread include the following[4,5]:

  • Dyspnea
  • Bone pain
  • Abdominal distention
  • Jaundice
  • Localizing neurologic signs
  • Altered cognitive function
  • Unexplained weight loss
  • Hypercalcemia
  • Increasing levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin
  • Rising levels of tumor markers (eg, carcinoembryonic antigen [CEA], CA15-3, CA27.29)
  • New, or increasing size of a preexisting, radiographic anomaly
  • New abnormal regions noted on functional imaging (eg, bone scan, PET/CT scan)
Image courtesy of Winston W Tan, MD.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Case 1

A 58-year-old cardiac nurse has a history of a 1.2 cm T1c, N0, M0 estrogen- and progesterone-receptor (ER/PR) positive, human epidermal growth factor receptor (HER2) positive (3+ by immunohistochemistry [IHC]) ductal carcinoma. She declined trastuzumab (owing to fear of the risk of congestive heart failure) but received 4 cycles of adriamycin and cyclophosphamide, underwent breast reconstruction, and then received tamoxifen for 10 years.

She presents for her scheduled follow-up. Her laboratory studies reveal a normal complete blood cell (CBC) count and CEA level, as well as elevated levels of cholesterol, thyroid stimulating hormone, and AST (64 IU/L).

Her abdominal CT scan is shown. What is the next step in the management of this patient?

  1. Obtain next generation sequencing.
  2. Biopsy the liver.
  3. Treat with chemotherapy.
  4. Treat with trastuzumab.
Image courtesy of Winston W Tan, MD.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Answer: B. Biopsy the liver.

"A liver mass is defined as a focal solid or cystic lesion that can be differentiated from the surrounding liver parenchyma by imaging techniques."[6] Widespread use of such imaging techniques for evaluating the abdomen has led to significantly greater identification and recognition of liver masses. The differential diagnosis is quite extensive, from benign asymptomatic lesions to malignant neoplasms, which may be diagnostically challenging for clinicians. Thus, obtaining a biopsy specimen from the liver with pathological analysis helps to determine the final diagnosis.[6]

Image from the National Cancer Institute (NCI).

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

The patient's liver lesions are biopsy proven to be ER/PR positive, HER2-positive adenocarcinoma that is consistent with breast cancer.

Which of the following is the best regimen for management of this patient?

  1. Paclitaxel and trastuzumab
  2. Pertuzumab and trastuzumab
  3. Pertuzumab, trastuzumab, and docetaxel
  4. Ado-trastuzumab and paclitaxel
Image courtesy of Winston W Tan, MD.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Answer: C. Pertuzumab, trastuzumab, and docetaxel

Management of HER2-positive metastatic breast cancer

About 20-25% of breast cancers are HER2-receptor positive.[7] HER2-directed treatments have been found to improve survival even in the metastatic setting.[7,8] First-line therapies for treatment-naive patients include monoclonal antibody therapy (trastuzumab, pertuzumab, ado-trastuzumab [TDM1, trastuzumab emtansine]) and/or tyrosine kinase inhibitor therapy (lapatinib) and/or chemotherapy with a taxane.[4,7,8] The American Society of Clinical Oncology (ASCO) recommends trastuzumab, pertuzumab, plus a taxane (eg, docetaxel, paclitaxel) for first-line treatment.[9]

Pertuzumab/trastuzumab/taxane therapy improves clinical outcomes compared with trastuzumab plus docetaxel.[4] Evidence to support this three-agent combination comes from a phase III trial of 808 women with HER2-positive metastatic breast cancer who were treated with trastuzumab (8 mg/kg loading dose, then 6 mg/kg intravenous [IV]) and docetaxel (75 mg/m2 IV), and then randomly assigned to treatment with pertuzumab (840 mg loading dose, then 420 mg) or placebo.[10] The results are shown above.

Adapted images from MedPix | ENS Scott Liu, Russell A Patterson, Uniformed Services University.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

On follow-up, restaging CT scanning shows an interval appearance of three new low-attenuation nodules in the right lobe of the liver (top row; bottom row, left image) which are suspicious for metastatic disease, as well as several new mixed lytic and sclerotic bony metastatic lesions (not shown). (Bottom right image: Well-defined lucencies in the right iliac bone in proximity to the sacroiliac joint.) No worrisome pulmonary nodules and no lymphadenopathy are noted.

The next step in the management of this patient should involve discontinuing the current treatment, and initiating which of the following treatments?

  1. Lapatinib/capecitabine
  2. Ado-trastuzumab
  3. Pertuzumab/trastuzumab
  4. Any of the above
  5. None of the above
Image from MedPix | ENS Scott Liu, Russell A Patterson, Uniformed Services University.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Answer: D. Any of the above[4,11-14]

ASCO recommends trastuzumab emtansine (ado-trastuzumab, TDM1) for second-line therapy.[9] For third-line treatment, other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) should be offered, and pertuzumab may be offered if not previously given.[9]

The addition of lapatinib to capecitabine is effective for women with HER2-positive, advanced breast cancer progression after treatment with anthracycline-, taxane-, and trastuzumab-based therapy.[11] Similarly, ado-trastuzumab improves overall survival (OS) in this population.[12,13] Finally, pertuzumab has been shown to be active beyond the first-line setting; the combination of pertuzumab/trastuzumab with or without a cytotoxic agent (eg, vinorelbine or a taxane) may be considered for those with disease progression following trastuzumab-based therapy without pertuzumab.[4,9,14,15]

Which of the following adjuvant therapy would you offer the patient in addition to her chemotherapy/targeted treatment for the bone metastasis?

  1. Calcium and vitamin D
  2. Alendronate
  3. Zoledronic acid
  4. Denosumab
  5. A, C, and D
Image from Guzik G. J Orthop Surg Res. 2016;11(1):54. [Open access.] PMID: 27125184, PMCID: PMC4848795.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Answer: E. A, C, and D

For patients with bone metastasis from breast cancer, denosumab and zoledronic acid have each been shown to reduce skeletal related events (SREs) (but there appears to be no impact on OS).[4] International practice guideline groups have not expressed a preference for either agent in the setting of metastatic breast cancer. However, although monthly denosumab may appear preferable to monthly zoledronic acid in terms of its modest SRE reduction, analgesic effects, and subcutaneous route of administration, the use of denosumab needs to be balanced with its increased direct drug costs.

Bisphosphonates should be used with calcium and vitamin D supplementation.[4]

The anteroposterior pelvic radiograph is from a patient with breast cancer metastasis to the proximal femur and the acetabulum.

Image courtesy of Winston W Tan, MD.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Case 2

A 65-year-old female with a negative family history of cancer presents with shortness of breath and a palpable breast mass.

Biopsy of the breast mass revealed evidence of carcinoma. Pathological analysis showed a 3.5-cm breast mass that had no necrosis and was ER positive, HER2 negative (1+ by IHC).

Her pulmonary CT scan is shown. Pleural fluid examination was consistent with breast adenocarcinoma with metastasis to the pleura. PET scanning revealed no evidence of metastasis in other body sites.

This patient was treated with paclitaxel for 4 months.

Image courtesy of Winston W Tan, MD.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Case 3

A 48-year-old-female presents with back pain. She states she was diagnosed with breast cancer in 2004 and underwent mastectomy, as well as received chemotherapy for approximately 8-9 months. One of the drugs may have been 5-fluorouracil (5-FU). She also took tamoxifen for approximately 11 years.

In 2017, she first developed back pain. Which of the following does the image show?

  1. Metastasis to the thoracic spine
  2. Metastasis to the intestines
  3. Metastasis to the liver
  4. Metastasis to the lungs
Image courtesy of Winston W Tan, MD.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Answer: A. Metastasis to the thoracic spine (The arrow indicates bone metastasis at T10.)

MRI of the thoracic spine demonstrated multifocal metastatic disease, and a PET scan revealed widespread osseous metastatic disease. There was no evidence of involvement of the lymph nodes, liver, or lungs. She received palliative radiotherapy to the spine with significant improvement in her back pain. Biopsy of several lesions showed HER2 negative, ER positive disease. She refused tamoxifen treatment and briefly received aromatase inhibitors with exemestane (estrogen modulator) and anastrozole (aromatase inhibitor); 6 months later, letrozole was initiated (aromatase inhibitor) because of arthralgia. She also received monthly denosumab.

The following year, her imaging scans showed disease progression with new metastases to the sacrum and ribs. Which of the following would be her best treatment option?

  1. Fulvestrant
  2. Fulvestrant and palbociclib
  3. Capecitabine
  4. Eribulin
  5. All of the above
Image from Nieder C, Pawinski A. Case Rep Oncol Med. 2014;2014:931546. [Open access.] PMID: 24716053, PMCID: PMC3970251.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Answer: B. Fulvestrant and palbociclib

Although all of the options are appropriate, hormonally targeted treatment is less toxic than chemotherapy and combination therapy with an estrogen blocker would further improve survival in this patient. Fulvestrant/palbociclib has been shown to improve progression-free survival (PFS) in hormone-receptor-positive, HER2-negative metastatic breast cancer that had progressed on previous endocrine therapy,[16] and it is an alternative for recurrent disease in this population.[4,17]

Estrogen antagonist treatment (ET) (alone or in combination with targeted agents) is generally less toxic than chemotherapy; it is preferable for most patients with hormone receptor-positive disease to begin treatment with ET, reserving chemotherapy for patients whose cancers appear to be either refractory to ET or which have extensive symptomatic visceral involvement. Several studies have suggested that the addition of targeted therapies to ET improves PFS, although OS results remain pending.[16,17] Agents used for such targeted therapies include everolimus or inhibitors of cyclin-dependent kinase (CDK)-4 and -6 (palbociclib, ribociclib, abemaciclib).

The abdominopelvic CT scan reveals hydronephrosis (white arrow) and bladder wall thickening (yellow arrow) (bladder catheter in situ) in an elderly patient with ER positive, HER2 negative recurrent breast cancer and metastasis to the urinary bladder.

Image from the NCI | Daniel Sone.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Palliative Care

Treatment of metastatic disease is palliative, with "the goal to anticipate, prevent, and reduce suffering," as well as to improve quality of life.[18,19] ASCO recommends considering the combination of palliative care with standard oncology care early in the treatment course for patients with metastatic cancer and/or a high symptom burden.[19] Specific recommendations are as follows[19]:

  • The time to start palliative care is as soon as a patient's cancer becomes advanced.
  • For newly diagnosed patients with advanced cancer, the Expert Panel suggests early palliative care involvement within 8 weeks after diagnosis.
  • Inpatients and outpatients with advanced cancer should receive dedicated palliative care services early in the disease course concurrent with active treatment.

Essential components of palliative care may include the following[19]:

  • Building rapport and relationships with patients and family caregivers (eg, cultural sensitivity, acknowledging patients' wishes)
  • Managing symptoms, distress, and functional status
  • Exploration of understanding and education about the illness and prognosis
  • Clarification of treatment goals
  • Assessment and support of coping needs (eg, provision of dignity therapy)
  • Assistance with medical decision making
  • Coordination with other care providers
  • Provision of referrals to other care providers as indicated
Image identifying a palliative approach in the literature from Sawatzky R, Porterfield P, Lee J, et al. BMC Palliat Care. 2016;15:5. [Open access.] PMID: 26772180, PMCID: PMC4715271.

Metastatic Breast Cancer: A Review of 3 Cases and Palliative Care

Winston W Tan, MD; Matthew Tan, BS Biomedical Science | February 12, 2019 | Contributor Information

Challenges and opportunities for improvement in transitioning to palliative care

Unfortunately, no clearly defined boundaries exist between curative and palliative care, and clinicians often don't have a plain grasp of what palliative care is.[20-22] Physicians may be unable to evaluate the futility of aggressive therapy, or they may be reluctant to communicate the incurableness of the condition to the patient and family caregivers.[22,23] Moreover, cultural, linguistic and/or religious differences may pose challenges.[22] Patients with advanced cancer also face difficult decisions, and they or relatives may not want to stop anti-cancer therapy.[22] Specific medications and/or a palliative care facility may be unavailable.[21,22]

Healthcare personnel involved in the care of patients with chronic and/or potentially fatal illnesses should learn about the basics of palliative care.[22,24] They can also improve their communication skills and strengthen patient/family participation in medical decision making.[20,23] Developing an integrative model that incorporates palliative care into the healthcare system as well as identifies potential medical, social, cultural, and geographic barriers would be a major step in overcoming many of the obstacles in transitioning from treatment to palliative care.[22-24]

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Advanced Breast Cancer: The Later Stages

Female breast cancer is the most common malignancy worldwide. Approximately 12.4% of US women will be diagnosed with breast cancer during their lifetime. Learn more about how to address this potentially deadly disease once it is no longer in the early stages.Slideshows, June 2017
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Breast Cancer

Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women. In less-developed countries, it is the leading cause of cancer death in women; in developed countries, however, it has been surpassed by lung cancer as a cause of cancer death in women.Diseases/Conditions, January 2019
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References