Imaging Analysis

65-year-old woman with sarcoidosis, suspicion of inflammatory breast carcinoma

The patient is a 65-year-old woman who presented to our institution with a biopsy-proven left breast cancer metastatic to the left axillary lymph node. Patient states that she first felt the left breast mass 5 months prior, and noted increase in its size. She denies any other palpable mass in the breast, no nipple discharge, or any other symptoms. Patient has sarcoidosis hypothyroidism, and a history of bilateral breast reductions. Her family history is pertinent for a sister who had breast cancer at the age of 49 years and a maternal aunt who also had breast cancer at the age of 42 years.

On physical exam, a 3-cm left breast mass, as well as an enlarged left axillary lymph node were palpated. There was noted skin thickening but no erythema or dermal edema (peau d’ orange) of the left breast.

The patient’s work up included a mammogram and sonogram of both breasts. The mammogram showed a superior central mass in the left breast measuring 3.8 cm with associated segmental microcalcifications – this correlated with the palpable mass. The sonogram confirmed the presence of the mass as well as a suspicious left axillary lymph node measuring 2.7 cm. The patient underwent a core biopsy of both the left breast mass and the left axillary lymph node that both showed poorly differentiated infiltrating ductal carcinoma with positive ER and PR receptors, and negative for HER2/neu. A staging PET/CT was then performed that showed hypermetabolic activity of both the left breast mass (measured 2.7 cm x 3.2 cm) and left axillary lymph node (measured 1.4 cm), some skin thickening overlying the left breast mass, a 0.6 cm internal mammary versus mediastinal node which was not hypermetabolic, and two subcentimeter nodules in the lungs that were too small to be characterized.

Steven K. Clinton, MD, PhDSteven K. Clinton, MD, PhD
Figure 1. (Clockwise from top left – CT image, PET image, whole body maximum intensity projection PET image, CT/PET fusion image) Hypermetabolic primary breast malignancy and hypermetabolic skin thickening (arrows). Figure 2. Hypermetabolic right axillary lymph node.

Steven K. Clinton, MD, PhD
The internal mammary vs. anterior mediastinal lymph node measuring less than 1 cm does not have significant focal hypermetabolic activity in this patient with a known history of sarcoidosis.

Photos courtesy of Munir Ghesani, MD

A skin punch biopsy was done in the office to rule out inflammatory breast cancer, and the pathology came back negative. At this point, the patient was staged T2N1M0 (stage IIB) left breast cancer. After a lengthy explanation of her treatment options, including pre-operative genetic testing, the patient opted for bilateral mastectomy with a left axillary lymph node dissection up-front, and then chemotherapy and hormonal therapy post-op. She refused any breast reconstruction. Surgical pathology confirmed inflammatory breast carcinoma.

Case Discussion

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which accounts for only 0.5-2% of breast cancer cases in the United States. Its incidence appears to be increasing, particularly among white women and it is being diagnosed at an earlier age. It is highly angiogenic and angioinvasive along with a very high metastatic potential. Because of the aggressiveness of the disease, the timing of the diagnosis is critical to direct appropriate therapy which will impact long-term survival outcomes. On physical exam, erythema and peau d’ orange of a third or more of the skin of the breast are usually present. A skin punch biopsy showing dermal lymphatic invasion (DLI) is confirmatory but not an absolute requirement for the diagnosis, since studies showed that despite adequate sampling, less than 75% of patients who had IBC showed DLI.

In 2008, the First International Conference on Inflammatory Breast Cancer was held in Houston, TX, and their consensus recommendations were published in the Annals of Oncology in 2011. A summary of their minimum recommendations is shown (See Table). Aside from reiterating that skin biopsy showing DLI is not an absolute requirement for diagnosis, and that clinical diagnosis is still the most important, the panel also made some recommendations with regard to diagnostic imaging of IBC. In summary, mammogram of the breast, and ultrasound of the breast and regional lymph nodes are still the recommended imaging studies. Key features in mammography are skin thickening and trabecular distortion. Ultrasound is a valuable tool in localizing mass or architectural distortions for biopsy. For staging, the panel recommends CT scan of the chest/abdomen/pelvis, and a bone scan. Breast MRI is only indicated in cases where the mammogram and ultrasound fail to identify an underlying breast parenchymal lesion. Data with regard to the use of PET/CT for staging are not sufficient at this time for the panel to recommend its use routinely.

Minimum Recommendations for Inflammatory Breast Carcinoma (IBC) Diagnosis

Neoadjuvant chemotherapy followed by locoregional treatment is the standard approach for IBC. However, the optimal chemotherapy regimen, including the sequence of agents and duration of treatment, is clearly undefined. Most clinicians use anthracycline- and taxane-based adjuvant chemotherapy regimens similar to those used for noninflammatory breast cancer. Anthracyclines and specifically taxanes are particularly effective in inflammatory breast cancer with initial response rates as high as 75% to 80%. Patients with inflammatory breast cancer and HER2 overexpression should receive HER2-directed therapy in conjunction with neoadjuvant chemotherapy for a total of 1 year. There are limited data on the role of adjuvant chemotherapy after neoadjuvant chemotherapy and appropriate locoregional treatment. Currently, there are multiple ongoing clinical trials examining the role of immunotherapy and monoclonal antibodies for the treatment of inflammatory breast cancer.

For a surgeon, diagnosing IBC pre-operatively is vital since treatment options greatly differ depending on the stage of the breast cancer. IBC is an automatic T4d stage – at least stage IIIB if nonmetastatic, and stage IV if metastatic. In the case presented, given a 3.8-cm left breast mass with metastasis to the ipsilateral axillary lymph node, patient is staged T2N1M0, stage IIB. Options for this stage (as per the NCCN Guidelines) include breast conservation therapy with axillary staging, up-front mastectomy with axillary staging and immediate breast reconstruction, or neoadjuvant chemotherapy with subsequent breast conservation therapy and axillary staging. However, a diagnosis of IBC (stage IIIB) is a contraindication to breast conservation therapy and to immediate breast reconstruction. Also, primary systemic chemotherapy should be the first-line treatment in IBC.

Pertinent to this case as well is genetic testing for BRCA 1 and 2 given the patient’s strong family history for breast cancer. If the patient did test positive, then an option for a contralateral prophylactic mastectomy will be given, as well as consideration for a bilateral oophorectomy given the increased risk of ovarian cancer with gene carriers.

Interesting to note in this case are the findings of nonhypermetabolic internal mammary versus mediastinal node and subcentimeter lung nodules on PET/CT which may be due to the patient’s underlying sarcoidosis. Without a baseline CT or PET/CT to prove their existence prior to the diagnosis of breast cancer, short of a biopsy, there is no way to confirm if they are indeed due to sarcoidosis or metastatic from the breast cancer. Although the suspicion might be lower in this case since the nodes/nodules are nonhypermetabolic, PET/CT has limitations in this application due to lower sensitivity of detection of disease (due to resolution limits) in subcentimeter lesions.

Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center, and Beth Israel Medical Center and a HemOnc Today section editor. He is an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons.

Karen Ching, MD is a breast surgery fellow at St Luke’s-Roosevelt and Beth Israel Hospitals.

Amit Patel, MD, is an oncology fellow at St. Luke’s-Roosevelt Hospital Center.

Sharon Rosenbaum Smith, MD, FACS, is an attending breast surgeon at St Luke’s-Roosevelt Hospital.

Earn CME this spring at the HemOnc Today Breast Cancer Review & Perspective meeting to be held March 23-24, 2012 at the Hilton San Diego Bayfront. See details at HemOncTodayBreastCancer.com.

For more information:

The patient is a 65-year-old woman who presented to our institution with a biopsy-proven left breast cancer metastatic to the left axillary lymph node. Patient states that she first felt the left breast mass 5 months prior, and noted increase in its size. She denies any other palpable mass in the breast, no nipple discharge, or any other symptoms. Patient has sarcoidosis hypothyroidism, and a history of bilateral breast reductions. Her family history is pertinent for a sister who had breast cancer at the age of 49 years and a maternal aunt who also had breast cancer at the age of 42 years.

On physical exam, a 3-cm left breast mass, as well as an enlarged left axillary lymph node were palpated. There was noted skin thickening but no erythema or dermal edema (peau d’ orange) of the left breast.

The patient’s work up included a mammogram and sonogram of both breasts. The mammogram showed a superior central mass in the left breast measuring 3.8 cm with associated segmental microcalcifications – this correlated with the palpable mass. The sonogram confirmed the presence of the mass as well as a suspicious left axillary lymph node measuring 2.7 cm. The patient underwent a core biopsy of both the left breast mass and the left axillary lymph node that both showed poorly differentiated infiltrating ductal carcinoma with positive ER and PR receptors, and negative for HER2/neu. A staging PET/CT was then performed that showed hypermetabolic activity of both the left breast mass (measured 2.7 cm x 3.2 cm) and left axillary lymph node (measured 1.4 cm), some skin thickening overlying the left breast mass, a 0.6 cm internal mammary versus mediastinal node which was not hypermetabolic, and two subcentimeter nodules in the lungs that were too small to be characterized.

Steven K. Clinton, MD, PhDSteven K. Clinton, MD, PhD
Figure 1. (Clockwise from top left – CT image, PET image, whole body maximum intensity projection PET image, CT/PET fusion image) Hypermetabolic primary breast malignancy and hypermetabolic skin thickening (arrows). Figure 2. Hypermetabolic right axillary lymph node.

Steven K. Clinton, MD, PhD
The internal mammary vs. anterior mediastinal lymph node measuring less than 1 cm does not have significant focal hypermetabolic activity in this patient with a known history of sarcoidosis.

Photos courtesy of Munir Ghesani, MD

A skin punch biopsy was done in the office to rule out inflammatory breast cancer, and the pathology came back negative. At this point, the patient was staged T2N1M0 (stage IIB) left breast cancer. After a lengthy explanation of her treatment options, including pre-operative genetic testing, the patient opted for bilateral mastectomy with a left axillary lymph node dissection up-front, and then chemotherapy and hormonal therapy post-op. She refused any breast reconstruction. Surgical pathology confirmed inflammatory breast carcinoma.

Case Discussion

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which accounts for only 0.5-2% of breast cancer cases in the United States. Its incidence appears to be increasing, particularly among white women and it is being diagnosed at an earlier age. It is highly angiogenic and angioinvasive along with a very high metastatic potential. Because of the aggressiveness of the disease, the timing of the diagnosis is critical to direct appropriate therapy which will impact long-term survival outcomes. On physical exam, erythema and peau d’ orange of a third or more of the skin of the breast are usually present. A skin punch biopsy showing dermal lymphatic invasion (DLI) is confirmatory but not an absolute requirement for the diagnosis, since studies showed that despite adequate sampling, less than 75% of patients who had IBC showed DLI.

In 2008, the First International Conference on Inflammatory Breast Cancer was held in Houston, TX, and their consensus recommendations were published in the Annals of Oncology in 2011. A summary of their minimum recommendations is shown (See Table). Aside from reiterating that skin biopsy showing DLI is not an absolute requirement for diagnosis, and that clinical diagnosis is still the most important, the panel also made some recommendations with regard to diagnostic imaging of IBC. In summary, mammogram of the breast, and ultrasound of the breast and regional lymph nodes are still the recommended imaging studies. Key features in mammography are skin thickening and trabecular distortion. Ultrasound is a valuable tool in localizing mass or architectural distortions for biopsy. For staging, the panel recommends CT scan of the chest/abdomen/pelvis, and a bone scan. Breast MRI is only indicated in cases where the mammogram and ultrasound fail to identify an underlying breast parenchymal lesion. Data with regard to the use of PET/CT for staging are not sufficient at this time for the panel to recommend its use routinely.

Minimum Recommendations for Inflammatory Breast Carcinoma (IBC) Diagnosis

Neoadjuvant chemotherapy followed by locoregional treatment is the standard approach for IBC. However, the optimal chemotherapy regimen, including the sequence of agents and duration of treatment, is clearly undefined. Most clinicians use anthracycline- and taxane-based adjuvant chemotherapy regimens similar to those used for noninflammatory breast cancer. Anthracyclines and specifically taxanes are particularly effective in inflammatory breast cancer with initial response rates as high as 75% to 80%. Patients with inflammatory breast cancer and HER2 overexpression should receive HER2-directed therapy in conjunction with neoadjuvant chemotherapy for a total of 1 year. There are limited data on the role of adjuvant chemotherapy after neoadjuvant chemotherapy and appropriate locoregional treatment. Currently, there are multiple ongoing clinical trials examining the role of immunotherapy and monoclonal antibodies for the treatment of inflammatory breast cancer.

For a surgeon, diagnosing IBC pre-operatively is vital since treatment options greatly differ depending on the stage of the breast cancer. IBC is an automatic T4d stage – at least stage IIIB if nonmetastatic, and stage IV if metastatic. In the case presented, given a 3.8-cm left breast mass with metastasis to the ipsilateral axillary lymph node, patient is staged T2N1M0, stage IIB. Options for this stage (as per the NCCN Guidelines) include breast conservation therapy with axillary staging, up-front mastectomy with axillary staging and immediate breast reconstruction, or neoadjuvant chemotherapy with subsequent breast conservation therapy and axillary staging. However, a diagnosis of IBC (stage IIIB) is a contraindication to breast conservation therapy and to immediate breast reconstruction. Also, primary systemic chemotherapy should be the first-line treatment in IBC.

Pertinent to this case as well is genetic testing for BRCA 1 and 2 given the patient’s strong family history for breast cancer. If the patient did test positive, then an option for a contralateral prophylactic mastectomy will be given, as well as consideration for a bilateral oophorectomy given the increased risk of ovarian cancer with gene carriers.

Interesting to note in this case are the findings of nonhypermetabolic internal mammary versus mediastinal node and subcentimeter lung nodules on PET/CT which may be due to the patient’s underlying sarcoidosis. Without a baseline CT or PET/CT to prove their existence prior to the diagnosis of breast cancer, short of a biopsy, there is no way to confirm if they are indeed due to sarcoidosis or metastatic from the breast cancer. Although the suspicion might be lower in this case since the nodes/nodules are nonhypermetabolic, PET/CT has limitations in this application due to lower sensitivity of detection of disease (due to resolution limits) in subcentimeter lesions.

Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center, and Beth Israel Medical Center and a HemOnc Today section editor. He is an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons.

Karen Ching, MD is a breast surgery fellow at St Luke’s-Roosevelt and Beth Israel Hospitals.

Amit Patel, MD, is an oncology fellow at St. Luke’s-Roosevelt Hospital Center.

Sharon Rosenbaum Smith, MD, FACS, is an attending breast surgeon at St Luke’s-Roosevelt Hospital.

Earn CME this spring at the HemOnc Today Breast Cancer Review & Perspective meeting to be held March 23-24, 2012 at the Hilton San Diego Bayfront. See details at HemOncTodayBreastCancer.com.

For more information: