Invasive lobular carcinoma: Clinical sciences

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Introduction0:00–0:54

Invasive lobular carcinoma is the second most common subtype of invasive breast cancer and occurs when malignant epithelial cells from lobular tissue infiltrate through their basement membrane.
It’s more common in older patients and more likely to be at an advanced stage on initial diagnosis. This cancer can be classified as early-stage, locally-advanced, or metastatic disease, and treatment is based on the stage.
As a clinical pearl, shared multi-disciplinary decision making is a central standard to breast cancer care, which is managed by a breast team that consists of a breast surgeon, oncologist, radiation oncologist, pathologist, radiologist, and reconstructive surgeon.When assessing a patient presenting with a new breast lump or abnormal finding, consider an invasive lobular carcinoma.

Initial assessment0:54–3:04

The first step is to obtain a focused history and physical exam, as well as labs like CBC, CMP, LFTs, and alkaline phosphatase.Typically, patients present with an abnormal screening mammogram or a new breast finding like a lump or asymmetric area of firmness.
The history might also include changes in breast or nipple appearance, nipple discharge, or axillary lymphadenopathy. Make sure to ask your patient about risk factors, such as the personal or family history of breast or ovarian cancer, early menarche, late menopause, nulliparity, or first pregnancy after 30 years of age.
Other important risk factors include age over 40, and alcohol use. Finally, look out for a known history of dense breast tissue, exogenous hormone use, as well as family or personal history of deleterious cancer gene mutations like BRCA.Physical exam might reveal a palpable breast mass and skin or nipple changes.
Now, lobular carcinomas are less likely to form a discrete mass, which makes them more difficult to detect on physical exam.
So, pay close attention to any areas that feel asymmetric or firm. Another important finding is lymphadenopathy.
When assessing lymph nodes, make sure to examine above and below the clavicle, and in the axilla. Also pay attention to findings that may indicate metastasis, such as bone pain, neurological changes, or a cough.
Finally labs might show elevated LFTs or alkaline phosphatase, potentially indicating metastasis to the liver or bone, respectively.
Once you’re done with history and physical exam, move on to imaging. To start, get a diagnostic mammogram and an ultrasound.

Imaging3:04–4:54

If neither of the imaging studies show any suspicious findings or evidence of underlying breast cancer, consider an alternative diagnosis.
Here’s a clinical pearl! Breast findings on imaging can be categorized with a standardized system called BI-RADS, which stands for Breast Imaging-Reporting and Data System.
The imaging findings are assigned into categories labeled as 0 to 6. First, 0 means incomplete, which needs additional imaging or comparison with previous images if available.
Next, 1 is negative, meaning that mammography is normal, with no findings like masses or calcification; while 2 indicates findings are completely benign, meaning that mammography reveals findings with no probability of malignancy; a category of 0, 1, and 2 can only be used when undergoing routine screening.
On the other hand, 3 is probably benign, meaning that mammography may reveal a finding with minimal malignant potential of less than 2%, so these patients should get follow-up imaging.
Next, 4 is suspicious for malignancy, meaning that mammography may reveal a finding with malignant potential between 2 to 94%, where biopsy will likely be indicated.
Then, a category of 5 is highly suspicious of malignancy, with malignant potential over 95%. Lastly, 6 is known malignancy that has been proven with biopsy, and requires definitive management with surgery, chemotherapy, or radiation.
Now, let’s talk about imaging findings that are suspicious for invasive lobular carcinoma. Lobular carcinoma can be multifocal and bilateral, so remember to always investigate both breasts.

Invasive lobular carcinoma4:54–6:14

A diagnostic mammogram might show a spiculated or irregular soft tissue opacity or mass. Due to their diffuse growth pattern, well-circumscribed masses are not as common, and it can be difficult to identify the extent of the disease.
In addition, imaging might show calcifications. However, in some cases, asymmetry or slight architectural distortion might be the only suspicious findings.
On ultrasound, look for a spiculated soft tissue mass of heterogeneous hypoechogenicity that’s taller than it’s wide, with posterior acoustic shadowing.
You might even see acoustic shadowing without a mass. In addition, ultrasound can help evaluate for abnormal lymph nodes, which will show an irregular shape, abnormal cortical thickening, or displaced fatty hilum.
If you encounter any of these signs, suspect invasive lobular carcinoma. Okay, after imaging, you need to confirm the diagnosis with a core needle biopsy.

Core needle biopsy6:14–7:14

If the core needle biopsy doesn’t show any malignant cells, and the biopsy results are consistent with the imaging findings, consider an alternative diagnosis.
However, if the core biopsy doesn't show findings that provide a diagnosis consistent with imaging, it could be a false negative, so you should repeat a core biopsy or even get an excisional biopsy!
Okay, histologic findings consistent with lobular carcinoma include small, uniform, malignant epithelial cells of lobular origin.
These cells are discohesive and diffusely infiltrate breast stroma in a single-file manner, which indicates loss of cellular E-cadherin.
Additionally, they might be encircling ducts. If you see these findings, you can diagnose invasive lobular carcinoma.After confirming the diagnosis, the next step is TNM staging.

TNM staging7:14–8:41

First, evaluate the tumor based on size and invasion into structures like skin or chest wall. Then, you want to evaluate lymph nodes.
If any nodes are palpable or suspicious on ultrasound, perform a fine needle aspiration biopsy of the node. In lobular carcinoma, also consider evaluation with breast MRI, to get a better idea of the tumor size.
Additional advanced imaging can be done for specific indications if the patient has clinical findings of metastasis, such as hemoptysis or bone pain.
Next, establish the tumor’s estrogen, progesterone, and HER2 receptor statuses. Lobular carcinomas are typically estrogen receptor-positive.
Additionally, some patients should meet with a genetic counselor to consider testing for inherited genetic mutations. A few high-risk criteria to remember include diagnosis at a young age, meaning 45 and under, certain ethnic groups like Ashkenazi Jews, triple-negative breast cancer, so negative for estrogen, progesterone, and HER2 receptors; as well as prior history of separate breast cancer, and a significant family history of breast or ovarian cancer.
Alright, next up is treatment, which depends on their clinical stage. Early-stage disease includes all stage one and most stage two cancers.

Early stage8:41–10:49

These tumors are T1 or T2, so they’re 5 centimeters or smaller in size, and don’t invade other structures; N0 or N1 nodal status, meaning that 0 to 3 lymph nodes are involved; and are M0, meaning that there’s no evidence of distant metastasis.
When it comes to treatment, surgical options include breast-conserving therapy, such as a partial mastectomy, also called lumpectomy, with radiation; or total mastectomy with or without breast reconstruction.
In general, patients can choose between surgical options according to their personal goals and values. However, breast-conserving therapy is contraindicated in multicentric disease, large tumor size in relation to the breast size, prior radiation therapy of the chest, and pregnancy.
Okay, the next consideration is the management of axillary lymph nodes. During the operation, the surgeon will perform a sentinel lymph node biopsy to look for malignant cells.
If the node biopsy is positive in at least 3 nodes, the patient needs an axillary lymph node dissection. On the other hand, patients with clinically palpable nodes on physical exam get axillary node dissection without sentinel biopsy.
After surgery, consider additional treatments. If nodes were positive, the patient will need adjuvant axillary radiation; while regardless of nodes, patients who underwent breast-conserving therapy with partial mastectomy will receive radiation therapy and adjuvant hormone and immunotherapies according to their tumor receptor status, such as a SERM like tamoxifen or an aromatase inhibitor like anastrozole.
Now let’s talk about locally-advanced cancer, which typically falls under stage three. These tumors are T3 or T4, meaning greater than 5 centimeters; N2 or N3, meaning 4 or more lymph nodes involved; and are M0, so no evidence of distant metastasis.

Locally-advanced10:49–12:26

If this is the case, consider full PET/CT body imaging and a bone scan to confirm there aren’t metastases. Then, start with neoadjuvant chemotherapy.
After chemotherapy is complete, reassess TNM staging to decide if they are candidates for breast-conserving therapy with partial mastectomy versus total mastectomy, as well as axillary node management.
Once the surgery is done, consider additional treatment options. Postoperative radiation therapy is performed in patients who underwent breast-conserving therapy and patients who had a total mastectomy with a tumor with a high risk of recurrence, such as those larger than 5 centimeters, positive margins, or extensive nodal involvement.
On the other hand, some patients require postoperative chemotherapy, while patients who fully completed neoadjuvant chemotherapy won’t need it.
Also, adjuvant systemic therapies like hormone or immunotherapy are started according to tumor receptor status. Lastly, let’s go over patients who have metastatic disease.
On TNM staging, they can have any T or N status but are M1, meaning they have distant metastasis. Invasive lobular carcinoma often metastasizes to unusual places, such as the ovaries, the gastrointestinal tract, and the peritoneum.

Metastatic12:26–13:39

Management should start with a biopsy of the metastatic lesion, if possible, to verify the tumor’s origin and assess for notable mutations.
Talk with the patient about treatment side effects, tumor progression, and goals of care to determine if palliative care is the best option.
You should offer palliative medical therapy to patients with metastatic disease to prolong survival and maximize quality of life.
This can include chemotherapy and other systemic therapies depending on the patient’s individual tumor biology. Additionally, assess your patient’s interest and candidacy for clinical trials.
Although most of these patients don’t undergo surgical resection, those with significant pain or local wounds might be candidates for palliative mastectomy.
Alright, as a quick recap… Patients with invasive lobular carcinoma commonly present after an abnormal screening mammogram or a breast lump, but due to its unique growth pattern, patients tend to present at advanced stages on initial diagnosis.
Start your diagnostic workup with a mammogram and ultrasound, and proceed with a core needle biopsy if you see suspicious findings on imaging.

Review13:39–14:30

Then, assess for clinically suspicious lymph nodes and obtain additional labs and imaging to determine the TNM staging. Next, establish the tumor’s estrogen, progesterone, and HER2 receptor status.
Finally, surgical, radiation, or systemic therapy depends on whether the patient has early-stage, locally-advanced, or metastatic disease.
see suspicious findings on imaging then assess for clinically suspicious lymph nodes and obtain additional labs and imaging to determine the TNM staging Next establish the tumors estrogen progesterone and her two receptor status Finally surgical radiation or systemic therapy depends on whether the patient has