
Advanced Breast Cancer: The Later Stages
The National Cancer Institute, on the basis of 2012-2014 data,[1] has estimated that approximately 12.4% of women will be diagnosed with breast cancer at some point during their lifetime. In 2014, an estimated 3,327,552 women were living with breast cancer in the United States.
Which of the following statements regarding breast cancer is true?
- It is the third most common cancer in females worldwide
- 5-year survival for all stages combined is approximately 90%
- Median age at diagnosis is 50 years
- Most tumors are metastatic at the time of diagnosis
Advanced Breast Cancer: The Later Stages
Answer: B. 5-year survival for all stages combined is approximately 90%.
Female breast cancer is the most common malignancy worldwide. In the United States, it is estimated that 252,710 new cases of female breast cancer will be diagnosed during 2017 and that 40,610 deaths will occur.[1] Median age at diagnosis of female breast cancer is 62 years. The 5-year overall survival is approximately 90% for all stages combined.
Advanced Breast Cancer: The Later Stages
The image in the slide shows a large exophytic mass in the left breast that is consistent with breast adenocarcinoma.
Which of the following statements regarding stage IV (metastatic) breast cancer is true?
- Fewer than 10% of breast cancers are stage IV at the time of diagnosis
- 5-year survival for stage IV breast cancer is approximately 5%
- The most common site of distant metastases is the abdominal cavity
- Metastatic breast cancer is twice as common in African Americans as it is in any other racial group
Advanced Breast Cancer: The Later Stages
Answer: A. Fewer than 10% of breast cancers are stage IV at the time of diagnosis.
Approximately 6% of newly diagnosed breast cancer cases have distant metastases at the time of diagnosis. In the United States, the 5-year relative survival for stage IV female breast cancer is 26.9%. The lungs and the skeleton are the most common sites of distant metastases. The incidence of metastatic cancer is similar in Caucasians and African Americans.[1]
Advanced Breast Cancer: The Later Stages
The mastectomy specimen in the slide shows a large breast adenocarcinoma.
Which of the following statements regarding systemic staging for newly diagnosed breast cancer is true?
- A systemic workup, including computed tomography (CT) of the chest, abdomen, and pelvis, should be done in all patients with newly diagnosed breast cancer
- Routine systemic imaging should be considered only in patients with stage III or IV tumors
- Magnetic resonance imaging (MRI) of the brain should be considered in patients with lymph node metastases, even in the absence of neurologic symptoms
- Bone scanning with technetium-99m is not sensitive for detecting skeletal metastases from breast cancer
Advanced Breast Cancer: The Later Stages
Answer: B. Routine systemic imaging should be considered only in patients with stage III or IV tumors.
According to the National Comprehensive Cancer Network (NCCN) guidelines, routine systemic imaging should be considered for staging of any breast cancer that is at least stage III at the time of diagnosis.[2] For patients with early-stage breast cancer, routine laboratory studies (eg, complete blood count [CBC], alkaline phosphatase, and liver function tests) are sufficient. However, if there are any specific symptoms or serum test result abnormalities, imaging studies should be considered. MRI of the brain should be considered in patients with neurologic symptoms. Bone scanning is highly sensitive for evaluating skeletal metastases from breast cancer.[3] The CT and positron emission tomography (PET) scans in the slide show metastatic tumor in the right scapula.
Advanced Breast Cancer: The Later Stages
The photograph in the slide shows an inflammatory right breast adenocarcinoma.
Which of the following statements about the workup of stage IV breast cancer is not true?
- HER2 testing of tumor cells should be performed in all metastatic breast cancers
- Hormone receptor (estrogen receptor [ER]/progesterone receptor [PR]) testing is not necessary, because it would not change the treatment options
- PET/CT can be selectively considered
- MRI of the brain can be considered in patients with neurologic signs or symptoms
Advanced Breast Cancer: The Later Stages
Answer: B. Hormone receptor (estrogen receptor [ER]/progesterone receptor [PR]) testing is not necessary, because it would not change the treatment options.
Hormone receptor testing should be performed on all patients with breast cancer, even if the cancer is stage IV at the time of diagnosis. Hormonal therapy (eg, with tamoxifen or anastrozole) is considered central to the management of hormone receptor–positive metastatic breast cancer. The micrograph in the slide shows breast cancer cells with positive immunostaining for ER. HER2 testing should also be performed; the results could alter treatment options. The use of advanced imaging studies such as PET or brain MRI should be considered selectively, depending on the specific clinical situation.
Advanced Breast Cancer: The Later Stages
Mammography is usually the initial test for the diagnosis of breast cancer. Any suspicious abnormality on screening mammography usually necessitates further evaluation. The mammograms in the slide depict suspicious breast lesions (left, red arrow; right, yellow markers).
Which of the following is the best next step in the management of a 6-cm (T3) biopsy-proven breast adenocarcinoma with matted axillary lymph nodes (N2)?
- Doxorubicin-based neoadjuvant chemotherapy
- Modified radical mastectomy
- Bilateral breast MRI
- CT of the chest, abdomen, and pelvis
Advanced Breast Cancer: The Later Stages
Answer: D. CT of the chest, abdomen, and pelvis.
By definition, breast cancer with matted or fixed axillary lymph nodes is classified as stage III. In this specific scenario, this T3N2 tumor would be assigned to stage IIIA. Management should begin with systemic staging to rule out distant metastatic disease. In the absence of distant metastases, most patients should receive neoadjuvant chemotherapy. Upfront surgery is reserved for very carefully selected cases and is not considered to be first-line therapy in the management of such patients. Breast MRI is not considered routine in the evaluation of breast cancer. The axial CT scan of the pelvis in the slide shows multiple bone metastases in a patient with breast cancer.
Advanced Breast Cancer: The Later Stages
The CT scans in the slide, obtained before (left) and after (right) injection of iodinated contrast material, show three brain metastases from breast cancer.
Which of the following is the best treatment option for triple-negative (ie, HER2–/ER–/PR–) stage IV breast adenocarcinoma?
- Doxorubicin-based chemotherapy
- Trastuzumab in combination with pertuzumab
- Tamoxifen
- Gemcitabine-based chemotherapy
Advanced Breast Cancer: The Later Stages
Answer: A. Doxorubicin-based chemotherapy.
Multiple accepted first-line chemotherapy options are available for the management of metastatic breast cancer. Doxorubicin-based chemotherapy is commonly used. Trastuzumab and pertuzumab, however, specifically target HER2-positive breast cancer and are not effective against triple-negative tumors. Tamoxifen is given to treat hormone receptor–positive tumors and thus is also inappropriate for triple-negative tumors. Gemcitabine is not used to treat breast cancer. The micrograph in the slide shows breast cancer metastasis to the liver.
Advanced Breast Cancer: The Later Stages
The image in the slide shows breast cancer metastases to the back.
Which of the following would be the best initial treatment option for a patient with a newly diagnosed ER/PR-positive, HER2-negative stage IV breast cancer?
- Endocrine therapy
- Pertuzumab-based chemotherapy
- Modified radical mastectomy followed by doxorubicin-based chemotherapy
- Whole-body radiation therapy
Advanced Breast Cancer: The Later Stages
Answer: A. Endocrine therapy.
According to national guidelines,[2] the first-line treatment for ER/PR-positive stage IV breast cancer, in the absence of visceral crisis, is endocrine therapy. Ovarian ablation or suppression, in addition to endocrine therapy, is performed in premenopausal women. Pertuzumab is considered for patients with HER2-positive breast cancer. Endocrine therapy usually consists of tamoxifen in premenopausal women and an aromatase inhibitor in postmenopausal women. Newer drugs, including palbociclib and ribociclib, have been approved for use, in combination with aromatase inhibitors, for advanced or metastatic hormone receptor–positive breast cancer in postmenopausal women. Surgery and radiation therapy play only a minimal role in the first-line management of metastatic breast cancer. The micrograph in the slide shows metastatic breast cancer to the stomach; immunohistochemistry is positive for ER (brown staining).
Advanced Breast Cancer: The Later Stages
The micrograph in the slide shows infiltrating breast adenocarcinoma with strong membrane immunoreactivity representing HER2/neu overexpression.
Which of the following is the best treatment option for HER2-positive, ER/PR-negative stage IV breast cancer?
- Doxorubicin-based chemotherapy
- Trastuzumab, pertuzumab, and taxane
- Tamoxifen
- Mitomycin C–based chemotherapy
Advanced Breast Cancer: The Later Stages
Answer: B. Trastuzumab, pertuzumab, and taxane.
Trastuzumab (shown) is a monoclonal antibody that targets the HER2/neu receptor and is commonly used in the treatment of HER2-positive breast cancer. Pertuzumab is another monoclonal antibody that also targets HER2. These two drugs, in combination with a taxane (eg, docetaxel), are considered first-line treatment for HER2-positive, hormone receptor–negative stage IV breast cancer.
Advanced Breast Cancer: The Later Stages
The coronal CT scan in the slide shows breast cancer metastasis to the right femur (red arrow).
A 64-year-old woman with hormone receptor–negative stage IV breast cancer has bone metastases. Which of the following drugs is recommended in addition to standard chemotherapy options?
- Calcium gluconate
- A bisphosphonate (eg, zoledronic acid)
- Raloxifene
- Dexamethasone
Advanced Breast Cancer: The Later Stages
Answer: B. A bisphosphonate (eg, zoledronic acid).
According to NCCN guidelines, breast cancer patients with bone metastases should receive bisphosphonate therapy in addition to standard treatment. Bisphosphonate therapy is associated with decreased occurrence of pathologic fractures and reduced need for radiation or surgical intervention. Renal function should be monitored.[4] Before initiation of therapy, patients should undergo a dental examination; osteonecrosis of the jaw can occur, albeit rarely. The optimal schedule for zoledronic acid is once monthly for a total of 12 doses and once quarterly thereafter. Calcium supplementation is usually in the form of calcium citrate. Raloxifene is a selective ER modulator and is not used to treat hormone receptor–negative breast cancer.[5] Steroids are sometimes given to decrease edema associated with cord compression from vertebral metastases; however, they are not routinely used for skeletal metastases. The image in the left part of the slide shows metastatic breast cancer in the right femur (red circle); the image in the right part shows a pathologic fracture at the site of a metastatic lesion.
Advanced Breast Cancer: The Later Stages
The image in the slide shows a very large ulcerated right breast adenocarcinoma.
A 59-year-old woman is found to have stage IV breast cancer. With chemotherapy, her metastatic disease is well controlled; however, she continues to have disabling symptoms of bleeding and infection from her large primary breast tumor.
Which of the following would be the most appropriate treatment option for this patient's primary breast tumor?
- Modified radical mastectomy
- Brachytherapy
- Photodynamic therapy
- Simple mastectomy
Advanced Breast Cancer: The Later Stages
Answer: D. Simple mastectomy.
Although surgery is not the first-line treatment option for patients with metastatic breast cancer, in cases where a patient is experiencing significant symptoms arising from a primary breast tumor, a palliative simple mastectomy (shown) may be considered for improvement of the patient's quality of life. However, such palliative procedures do not improve survival outcomes.[6] Modified radical mastectomy would subject the patient to an unnecessary axillary lymphadenectomy and hence would not be a good option. Brachytherapy and photodynamic therapy also would not be good options, in that they would not be able to alleviate the symptoms arising from a large primary tumor.
Advanced Breast Cancer: The Later Stages
The sagittal CT scan in the slide shows multiple bony metastases to the spine (yellow arrows) in a patient with metastatic breast cancer.
Which of the following is the most viable option for the management of spinal compression from vertebral breast cancer metastases?
- External-beam radiation therapy
- Brachytherapy
- Immunotherapy
- Double-dose chemotherapy
Advanced Breast Cancer: The Later Stages
Answer: A. External-beam radiation therapy.
Management of spinal compression from breast cancer metastases requires a multidisciplinary approach. Surgery, percutaneous kyphoplasty, and external-beam radiation therapy are all suitable options for palliation of symptoms and prevention of pathologic fractures.[7,8] The role of immunotherapy in breast cancer is still investigational. Brachytherapy has no role in this setting. Double-dose chemotherapy is not advisable, because of possible toxicities. The image in the left part of the slide shows an unstable spinal metastasis (yellow arrow); the image in the right part is from the same patient after surgical fixation of the spine.
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