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.
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
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
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
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
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
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.
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