Invasive Lobular Carcinoma

1 What is Invasive Lobular Carcinoma?

Invasive lobular carcinoma (ILC), sometimes called infiltrating lobular carcinoma, is the second most common type of breast cancer after invasive ductal carcinoma (cancer that begins in the milk-carrying ducts and spreads beyond it).

According to the American Cancer Society, more than 180,000 women in the United States find out they have invasive breast cancer each year. About 10% of all invasive breast cancers are invasive lobular carcinomas. (About 80% are invasive ductal carcinomas.)

Invasive means that the cancer has “invaded” or spread to the surrounding breast tissues. Lobular means that the cancer began in the milk-producing lobules, which empty out into the ducts that carry milk to the nipple. All together, “invasive lobular carcinoma” refers to cancer that has broken through the wall of the lobule and begun to invade the tissues of the breast. Over time, invasive lobular carcinoma can spread to the lymph nodes and possibly to other areas of the body.

Although invasive lobular carcinoma can affect women at any age, it is more common as women grow older. According to the American Cancer Society, about two-thirds of women are 55 or older when they are diagnosed with an invasive breast cancer. ILC tends to occur later in life than invasive ductal carcinoma — the early 60s as opposed to the mid- to late 50s.

Some research has suggested that the use of hormone replacement therapy during and after menopause can increase the risk of ILC.

2 Symptoms

At first, invasive lobular carcinoma may not cause any symptoms. Sometimes, an abnormal area turns up on a screening mammogram (X-ray of the breast), which leads to further testing.

Invasive lobular carcinomas tend to be more difficult to see on mammograms than invasive ductal carcinomas are. That’s because instead of forming a lump, the cancer cells more typically spread to the surrounding connective tissue (stroma) in a line formation.

In other cases, the first sign of ILC is a thickening or hardening in the breast that can be felt, rather than a distinct lump. Other possible symptoms include

  • an area of fullness or swelling,
  • a change in the texture of the skin,
  • the nipple turning inward.

According to the American Cancer Society, any of the following unusual changes in the breast can be a first sign of breast cancer, including invasive lobular carcinoma:

  • swelling of all or part of the breast
  • skin irritation or dimpling
  • breast pain
  • nipple pain
  • redness, scaliness, or thickening of the nipple or breast skin
  • a nipple discharge other than breast milk
  • a lump in the underarm area
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3 Causes

It's not clear what exactly causes invasive lobular carcinoma.

A number of gene faults are found that significantly increase a woman's risk of breast cancer. They are in the TP53 and PTEN genes. Genetic tests are available to women with a high risk of having changes in these genes

  • BRCA1
  • BRCA2
  • TP53
  • PTEN genes

Researchers have found other faults in common genes that can slightly increase a woman's risk of developing breast cancer. No tests are available for these genes yet but they include

  • CASP8
  • FGFR2
  • TNRCP
  • MAP3K1
  • rs4973768
  • LSP1

Rare genes that can also have faults and increase breast cancer risk slightly include

  • CHEK2
  • ATM (ataxia telangiectasia mutated)
  • BRIP1
  • PALB2

No individual tests are available for these genes yet. But if you are having a test for faulty BRCA genes they may find changes in one of these genes.

4 Making a Diagnosis

Diagnosing invasive lobular carcinoma usually involves a combination of procedures, including a physical examination and imaging tests. ILC tends to be multifocal, meaning that there is more than one area of cancer within the breast.

Some studies have shown that ILC is also more likely to affect both breasts (called bilateral cancer) than other types of invasive breast cancer.

Procedures for diagnosing ILC can include:

Physical examination of the breasts

Your doctor may be able to feel a thickening or hardening in the breast during a physical examination. With invasive lobular carcinoma, this is a more common finding than a distinct lump. He or she also will feel the lymph nodes under the armpit and above the collarbone to see if there are any swelling or other unusual changes.

Mammography

Invasive lobular carcinoma may be found by mammography, a test that obtains X-ray images of the breast. Mammograms are used to screen apparently healthy women for early signs of breast cancer.

However, ILC does not always show up well on a mammogram because of the cells’ tendency to grow in a single-file line, rather than form a mass. If mammogram does find invasive lobular carcinoma, the tumor may appear smaller than it actually is.

Whenever a screening mammogram highlights an area of concern, additional mammograms often will be done to gather more information about that area. Mammography will be performed on both breasts.

Ultrasound

Ultrasound bounces sound waves off of the breast to create additional images of the tissue. Ultrasound can be used in addition to mammography.

Ultrasound appears to be more accurate in detecting invasive lobular carcinoma than mammography is. As with mammography, however, the tumor may appear smaller than it actually is.

Breast MRI

MRI, or magnetic resonance imaging, uses magnetic fields, radio waves, and a computer to obtain images of tissues inside the body. In selected cases, a doctor may use breast MRI to gather more information about a suspicious area within the breast.

Biopsy

If you do have a suspicious mammogram or other imaging test result, your doctor will probably want you to have a biopsy. A biopsy involves taking out some or all of the abnormal-looking tissue for examination by a pathologist (a doctor trained to diagnose cancer from biopsy samples) under a microscope.

When possible, a doctor will usually use one of the quicker, less invasive approaches to biopsy. These include the following tests:

Fine needle aspiration biopsy

A very small, hollow needle is inserted into the breast. A sample of cells is removed and examined under the microscope. This method leaves no scars.

Core needle biopsy

A larger needle is inserted to remove several cylinder-shaped samples of tissue from the area that looks suspicious. In order to get the core needle through the skin, the surgeon must make a tiny incision. This leaves a very tiny scar that is barely visible after a few weeks.

In cases where the doctor cannot feel the lump, he or she may need to use ultrasound or mammograms to guide the needle to the right location. You may hear this referred to as stereotactic needle biopsy or ultrasound-guided biopsy.

If a needle biopsy is not able to remove cells or tissue, or it does not give definite results (inconclusive), a more involved biopsy may be necessary. These biopsies are more like regular surgery than needle biopsies:

Incisional biopsy

Incisional biopsy removes a small piece of tissue for examination.

Excisional biopsy

Excisional biopsy attempts to remove the entire suspicious lump of tissue from the breast.

Again, if the doctor cannot feel the lump, he or she may need to use mammography or ultrasound to find the right spot. Your doctor also may use a procedure called needle wire localization. Guided by either mammography or ultrasound, the doctor inserts a small hollow needle through the breast skin into the abnormal area. A small wire is placed through the needle and into the area of concern, and then the needle is removed. The doctor can use the wire as a guide in finding the right spot for biopsy.

The tissue samples are sent to a pathologist for examination under a microscope. The pathologist looks for the cell appearance and growth patterns that are typical of invasive lobular carcinoma. He or she may also order a special test called an E-cadherin protein study.

E-cadherin, or CDH1, is a gene that controls the activity of a protein that keeps cancer cells from spreading into normal, healthy tissue. A mutation, or unusual change, in the CDH1 gene can cause this gene to “turn off.” Some researchers feel that turning off CDH1 might cause ILC to develop.

Testing invasive lobular carcinoma cells for this mutation can help distinguish it from LCIS (lobular carcinoma in situ), a group of abnormal cells in the lobule that are not cancer. Rather, LCIS is considered to be an indication that someone is at increased risk of developing breast cancer. Most invasive lobular carcinomas do have some areas of LCIS within them.

The surgical biopsies are done only to make the diagnosis. If invasive lobular carcinoma is diagnosed, more surgery is needed to ensure all of the cancer is removed along with “clear margins,” which means that a border of healthy tissue around the cancer is also removed. Usually this means having lumpectomy or, in some cases, mastectomy.

Additional tests will be done on the tumor tissue to gather more information about how the cancer is likely to behave and what treatments will be most effective. Examples include:

Grade

A pathologist examines the cancer cells under a microscope and determines how abnormal they look and behave when compared with healthy breast cells. The lower the grade, the more closely the cancer cells resemble normal cells, the more slowly they grow, and the less likely they are to spread. There are three grades of invasive lobular carcinoma: low or grade 1; moderate or grade 2; and high or grade 3.

Grade 1 ILC cells, which are sometimes called “well-differentiated,” look and act somewhat like healthy breast cells. Grade 3 cells, also called “poorly differentiated,” are more abnormal in their behavior and appearance.

Surgical margins

When cancer cells are removed from the breast, the surgeon tries to take out the whole cancer with an extra area or “margin” of normal tissue around it. This is to be sure that all of the cancer is removed. The tissue around the very edge of what was removed is called the margin of resection. It is looked at very carefully to see if it is clear of cancer cells.

The pathologist also measures the distance between the cancer cells and the outer edge of the tissue. Margins around a cancer are described in three ways:

Negative

No cancer cells can be seen at the outer edge. Usually, no more surgery is needed.

Positive

Cancer cells come right out to the edge of the tissue. More surgery may be needed.

Close

Cancer cells are close to the edge of the tissue, but not right at the edge. More surgery may be needed.

What are called “negative” (or “clean”) margins can be different from hospital to hospital. In some places, doctors want at least 2 millimeters (mm) of normal tissue beyond the edge of the cancer. In other places, doctors may define a “clean margin” as less than 2 mm or more than 2 mm of healthy tissue. You may want to ask your doctor how your hospital defines clean margins.

To help standardize the definition of negative margins, the American Society for Radiation Oncology and the Society of Surgical Oncology issued new guidelines in February 2014 saying that clear margins, no matter how small as long as there was no ink on the cancer tumor, should be the standard for lumpectomy surgery.

Hormone receptor assay

This tissue test determines whether or not the breast cancer has receptors for the hormones estrogen and progesterone. A positive result means that estrogen or progesterone (or both) has the ability to fuel the cancer cells’ growth.

If the cancer is hormone-receptor-positive, your doctor likely will recommend hormonal therapies that block the effects of estrogen or lower estrogen levels in the body. Examples include tamoxifen and aromatase inhibitors.

If you are premenopausal, your doctor may discuss other options, such as using medications to shut down your ovaries temporarily, or even surgically removing them. The ovaries are the body’s main source of estrogen before menopause.

“Classic” or typical invasive lobular carcinoma is usually estrogen- and progesterone-receptor-positive.

HER2-receptor status

Another test is done to find out whether the breast cancer cells make too much of a protein called HER2 (human epidermal growth factor receptor 2). If they do, then they also have too many HER2 receptors at the cell surface.

With too many receptors, breast cancer cells pick up too many growth signals and start growing too much and too fast.

One way to slow down or stop the growth of the cancer cells is to block the receptors so they don't pick up as many growth signals. That’s what the medication called Herceptin (chemical name: trastuzumab) does. About 1 out of 4 breast cancers are HER2-positive, which means they can be treated with Herceptin.

HER2-positive cancers also can be treated with Tykerb (chemical name: lapatinib), a medication that interferes with the activity of HER2 from inside the cell. Tykerb limits the amount of energy the breast cancer cells have to grow and multiply.

Classic invasive lobular carcinoma is usually HER2-negative, however, meaning that Herceptin and Tykerb would not be used as treatments.

These tests are done on the tissue that is removed during biopsy, or, in the case of surgical margins, after the surgery to treat the cancer.

5 Treatment

Several treatment methods exist for invasive lobular carcinoma.

Surgery

Surgery is usually the first treatment for invasive lobular breast cancer. This may be breast-conserving surgery (the removal of the cancer and an area of normal breast tissue around the cancer) or a mastectomy (the removal of all the breast tissue and nipple area).

The type of surgery recommended will depend on

  • the area of the breast affected,
  • the size of the cancer compared to the size of your breast,
  • whether more than one area in the breast is affected.

If breast-conserving surgery is being considered, an MRI scan may be recommended to assess the size of the cancer (if you haven’t already had one to confirm the diagnosis). Your breast surgeon will discuss this with you.

Even after an MRI scan it can sometimes be difficult to estimate the size of an invasive lobular breast cancer before surgery. Because of this, some women who have breast-conserving surgery may need a second operation.

This is to ensure all the cancer, and a margin (border) of normal breast tissue around it, has been removed. In some cases, a mastectomy will be recommended as the second operation.

If you have invasive lobular breast cancer in more than one area of the breast, the surgeon may recommend a mastectomy. However, this will depend on the position of the areas affected and the size of your breast.

If a mastectomy is recommended, or if you choose to have a mastectomy, you will usually be able to have breast reconstruction. This can be done at the same time as your mastectomy (immediate reconstruction) or sometime in the future (delayed reconstruction).

Surgery to the lymph nodes

Your doctors will also want to check whether breast cancer cells have spread from the breast to the lymph nodes (glands) under the arm. This will help them decide whether you will need additional treatment after surgery.

To do this, your surgeon is likely to recommend an operation to remove either some (a lymph node sample or biopsy) or all of the lymph nodes (a lymph node clearance).

A widely used method for checking these lymph nodes is called sentinel lymph node biopsy. Sentinel lymph node biopsy isn’t suitable for everyone, and your surgeon will discuss whether it’s an option for you.

If the results of the sentinel lymph node biopsy show that the first node (or nodes) are affected you may be recommended to have further surgery or radiotherapy to the remaining lymph nodes.

What are the adjuvant (additional) treatments?

After surgery you may need further treatment. This is called adjuvant (additional) therapy and includes chemotherapy, radiotherapy, hormone therapy and targeted therapies. Which treatment you have will depend on your individual situation.

The aim of these treatments is to reduce the risk of breast cancer cells returning in the same breast or developing in the other breast – or spreading somewhere else in the body.

Sometimes chemotherapy or hormone therapy may be given before surgery. This is known as neo-adjuvant or primary therapy.

Chemotherapy

Chemotherapy is recommended for some people. This will depend on various features of the cancer, such as its size, its grade (how quickly the cells are dividing and how different they are to normal breast cells) and whether the lymph nodes are affected.

Radiotherapy

If you have breast-conserving surgery, you will usually be given radiotherapy to reduce the risk of the breast cancer returning in the same breast. Sometimes you may be offered radiotherapy to the nodes under your arm.

If you have a mastectomy, you may be given radiotherapy to the chest in the area where you had your surgery. This may be the case if the tumour was large, if there’s a high risk that cancer cells may have been left behind or if cancer cells are found in the lymph nodes under the arm (axilla).

Hormone (endocrine) therapy

As the hormone oestrogen can play a part in stimulating some breast cancers to grow, there are a number of hormone therapies that work in different ways to block the effect of oestrogen on cancer cells.

Hormone therapy will only be prescribed if your breast cancer has receptors within the cell that bind to the hormone oestrogen (known as oestrogen receptor positive or ER+ breast cancer). All breast cancers are tested for oestrogen receptors using tissue from a biopsy or after surgery.

When oestrogen binds to these receptors, it can stimulate the cancer to grow. If your cancer is oestrogen receptor positive, your specialist will discuss with you which hormone therapy they think is most appropriate.

Targeted therapies

Targeted therapies block the growth and spread of cancer. They target and interfere with processes in the cells that cause cancer to grow. The most widely used targeted therapy is trastuzumab (Herceptin).

Only people whose cancer has high levels of HER2 (HER2 positive or HER2+), a protein that makes cancer cells grow, will benefit from having trastuzumab.

6 Prevention

There is no absolute way to prevent invasive lobular carcinoma.

Risk factors increase a person’s chance of getting cancer. There are different kinds of risk factors. Some risk factors for cancer, like age and family history, cannot be prevented.

There are some risk factors that have been shown to increase the risk for invasive lobular carcinoma (ILC). Just because you have one or more of these risks does not mean you will get cancer.

  • Aging. Risk of developing breast cancer increases as women age.
  • Family history. Having a family history of breast cancer does increase your risk of developing breast cancer.
  • Benign breast conditions. Women with a history of multiple breast biopsies or a breast biopsy showing atypical cells may have an increased risk of developing breast cancer compared to patients who do not have this history.
  • Being BRCA1 or BRCA2 positive.
  • Being obese.
  • Being pregnant for the first time after the age of 30.
  • Taking certain hormone replacement therapy (HRT) after menopause
  • Women with cancer in one breast have a three- to four-fold increased risk of developing cancer in the other breast or in another part of the same breast

Speak with your physician if you believe you are at an increased risk for ILC.

Risk Reduction and Prevention

While there is no absolute way to prevent breast cancer, it is recommended that everyone receive age-appropriate screenings and live a healthy lifestyle by eating a balanced diet and exercising regularly.

Women should also know the symptoms and warning signs of breast cancer.

Women should talk with their doctor about specific preventive measures they can take.

As with most cancers, knowing the family history of breast cancer can help patients take action toward prevention, including:

  • Changing those risk factors that can be changed. Limit alcohol intake, exercise regularly, and maintain a healthy body weight. Women who choose to breast-feed for at least several months may also get an added benefit of reducing their breast cancer risk.
  • Find breast cancer early. Follow early detection guidelines to help find cancers when the likelihood of successful treatment is greatest.
  • Women who are or may be at increased risk can take steps to reduce their chances of developing breast cancer. These women should speak with their doctor to understand the risk and benefits of these steps.
  • Breast cancer chemoprevention, using drugs such as tamoxifen, raloxifene and aromatase inhibitors.
  • Preventive (prophylactic) bilateral mastectomy.

7 Lifestyle and Coping

Lifestyle modifications are necessary in order to cope with invasive lobular carcinoma.

To help yourself better cope with the side effects of breast cancer treatment and to reduce your chances of breast cancer recurrence, try incorporating these healthy tips:

Take care of yourself emotionally

  • Put your needs first sometimes
  • Attend a support group or find a breast cancer survivor you can talk with
  • Stay informed about new breast cancer research
  • Consider psychotherapy and/or antidepressants if warranted; if you’re taking tamoxifen, check with your oncologist to ensure the prescribed antidepressant does not interfere with your endocrine treatment
  • Communicate with your doctor about fears or concerns
  • Volunteer or become a breast cancer advocate

Take care of yourself physically

  • Exercise regularly
  • Maintain a healthy weight
  • Reduce stress
  • Eat healthy
  • Limit alcohol consumption
  • Keep up with all scheduled screenings
  • Quit smoking
  • Report any physical changes to either your oncologist or primary care provider
  • Seek treatment for lymphedema if you experience signs

Eat healthy

Research has shown that a diet high in fat and calories increases circulating estrogen in the blood. Consuming a low fat and low calorie diet after breast cancer can improve your overall health and wellness. Here are some dietary suggestions:

  • Eat a diet rich in fruits and vegetables (at least five servings a day)
  • Choose organic foods whenever possible
  • Wash produce thoroughly to minimize pesticide exposure
  • Limit red meat intake
  • Consume 2-3 servings of fish weekly. Fish high in omega-3 fatty acids, such as salmon or sardines, are especially beneficial (try to consume freshwater wild salmon whenever possible)
  • Increase fiber intake
  • Avoid trans fat

Reduce stress

As a breast cancer survivor, your life has probably been filled with stress for some time now. The good news is that life will eventually calm down for you and your family.

That does not mean the stress with coping with being a breast cancer survivor in combination with life’s everyday stress will not be a challenge. Finding ways to limit or cope with stress has been shown to improve overall survival.

Just as every woman’s body is different, so is her ability to cope with stress. It is important that you find practical ways to cope with stress that work for you and your lifestyle.

Some helpful techniques for relieving stress include:

  • Exercise
  • Support groups
  • Acupuncture
  • Journaling
  • Mental health counseling
  • Exploring your creative abilities (such as painting, drawing or ceramics)
  • Gardening
  • Massage therapy
  • Energy healing (such as Reiki)
  • Yoga
  • Meditation and deep breathing exercises
  • Guided imagery
  • Take a cancer vacation to celebrate how far you have come
  • Discover new connections (such as religious/spiritual groups, reconnecting with friends, or new hobbies)
  • Be patient in finding your “new normal”
  • Reflect on the meaning of cancer and the experiences it has brought into your life—both good and bad
  • Find strength in your “wounds”

If stress or depression seems to be impacting your overall quality of life, speak to your doctor.

Limit alcohol

Research has shown a link between moderate and heavy drinking and breast cancer. High alcohol intake has also been shown to increase circulating estrogen levels in the body.

Breast cancer survivors should limit their alcohol intake to a maximum of one drink a day to reduce the chance of a recurrence.

Exercise regularly

Exercising regularly improves fatigue symptoms, reduces stress, and impacts long-term overall health. The ten-year survival rate is higher in patients who exercise regularly than in patients who do not. We recommend that you engage in moderate exercise at least 3-5 hours per week.

Continue with regular health screenings

In addition to mammograms, you should stay up to date on

  • flu shots and other vaccinations;
  • screening colonoscopies;
  • pap smears;
  • bone density scans (if you’re over age 50 or no longer menstruating after chemotherapy);
  • annual physicals by your primary care provider;
  • dental cleanings;
  • cholesterol, diabetes and blood pressure screening to monitor your risk for cardiovascular disease;
  • any other screenings your doctor recommends.

Maintain a healthy weight

Women who are overweight are more likely to have their breast cancer come back. Maintaining a healthy weight is something you can do to reduce your chance of a recurrence as well as optimize your overall health.

Have your vitamin D levels checked

It is not known yet if taking vitamin D supplements after breast cancer will reduce your chances of recurrences in the future. However, next time you have blood work performed you may want to ask your medical provider to check your vitamin D levels for general health reasons.

Taking a supplement and/or spending 20 minutes outside in the sunshine every day will help increase your vitamin D3 levels. For women experiencing bone, joint or muscle pain on aromatase inhibitors, studies are being done to find out if vitamin D supplements at higher doses would be helpful.

You should always speak with your doctor before starting higher doses of any vitamins or nutritional supplements, since most are not regulated by the U.S. Food and Drug Administration.

Take endocrine therapies as prescribed

It’s very important to take your endocrine therapy drug exactly as prescribed. Research has shown that many women do not—usually because of forgetfulness, cost or undesirable side effects. When not taken as intended, many endocrine therapy drugs are less effective and may create other health problems.

If cost or side effects are a concern, speak to your oncologist. Many pharmaceutical companies offer financial assistance programs and there are a variety of ways to manage symptoms.

8 Risks and Complications

The list of complications that have been mentioned in various sources for Invasive lobular carcinoma includes:

Complications of Invasive lobular carcinoma are secondary conditions, symptoms, or other disorders that are caused by Invasive lobular carcinoma.

In many cases the distinction between symptoms of Invasive lobular carcinoma and complications of Invasive lobular carcinoma is unclear or arbitrary.

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