When asked what the number one risk factor for breast cancer is, founder and chief scientist of ZRT Laboratory Dr. David Zava has been known to say, “wearing a bra.”

He's right. Why? Because having breasts, or just being a woman, is indeed the biggest risk factor, since the disease is 100 times more common in women than in men.

This is Breast Cancer Awareness month, but given the controversies that continue to rage about the benefits of screening (for example, a mammogram may not pick up the most invasive and deadly types of breast cancer) it seems appropriate to step back and look at what breast cancer really is, what it is not, and who is at the most risk. 

What Breast Cancer Is Not

Breast cancer is not the leading cause of death in women, or even the leading cause of cancer death. The most prevalent cause of death in women, responsible for 1 out of every 4 deaths, is heart disease. While all types of cancer come a close second to heart disease as a cause of death, in both men and women the leading cause of cancer death is lung cancer, which accounts for a whopping 25% of those cancer deaths. Breast cancer is the second leading cause of cancer death in women, accounting for 15% of all cancer deaths.

It’s important also to understand that breast cancer is not just one disease. There are many types, with different attributes and degrees of invasiveness. When a breast tumor is confined to the breast, it doesn’t kill you. Cancer only becomes deadly when it invades other tissues and organs, in a process called metastasis. One common type of breast cancer, ductal carcinoma in situ (DCIS), accounts for 1 in 5 new breast cancer diagnoses; it is not invasive, easily picked up on a routine mammogram, and can be completely cured.

What Breast Cancer Is

Let’s look at the most common types of breast cancer and some of their attributes.

1. Invasive ductal carcinoma (IDC)
The most common type of breast cancer, accounting for 80% of invasive breast tumors, IDC originates in the milk ducts within the breast, invades through the wall of the duct, and grows into the fatty breast tissue. It can be detected early via a routine mammogram. If left untreated, it can invade further into the lymph nodes in the armpits, and then metastasize to other parts of the body via the lymphatic system and bloodstream.

2. Ductal carcinoma in situ (DCIS)
As the name suggests, this involves the cells lining the milk ducts, which become cancerous; however, they remain “in situ” so they have not spread through the duct walls into the surrounding breast tissue. It is completely cured by treatment, but if left untreated it may develop into invasive cancer. It accounts for 20% of new breast cancer diagnoses.

3. Lobular carcinoma in situ (LCIS)
Similar to DCIS, but in this case the cancer cells form in the lobules of the breast’s milk-producing glands and do not invade the walls of the lobules. It differs from DCIS in that it does not become invasive if left untreated. However, women with LCIS are at a 7-11 fold increased risk of developing invasive breast cancer, and should be sure to have regular checkups and mammograms.

4. Invasive lobular carcinoma (ILC)
Like LCIS, ILC begins in the lobules, and like IDC it can metastasize to other parts of the body. It is harder to detect via a mammogram than IDC, but is rarer, accounting for only 10% of invasive breast cancers.

5. Inflammatory breast cancer
Although accounting for only 1 to 3% of all breast cancers, inflammatory breast cancer is particularly problematic as it has a greater chance of spreading throughout the body than IDC or ILC. It is hard to detect early because it is often mistaken for a breast infection, and does not show up on a mammogram because there is no actual lump in the breast. Instead, the cancer cells block lymph vessels in the skin of the breast, which looks red, feels warm, and can have a pitted appearance like orange peel.

6. Paget's disease of the nipple
This is almost always associated with either DCIS or IDC and often requires mastectomy. It begins in the milk ducts and spreads to the nipple and then the areola, which appear crusted, scaly, and red, and can bleed or ooze. It accounts for only 1% of all breast cancer cases.

Triple-Negative Breast Cancer

There are multiple, rare types of breast cancer, usually sub-types of IDC, which have unique attributes. But breast cancers are also classified according to hormone receptor status, and the least common type under this classification is known as “triple-negative breast cancer” because it is made up of cancer cells that lack estrogen and progesterone receptors and do not have excess surface HER2 protein. To understand triple-negative breast cancer and why it is harder to treat, we need to look at the implications of hormone receptors and HER2 for breast cancer treatment.

About 75% of breast cancers are estrogen receptor (ER) positive, and proliferate in response to estrogen; about 65% of ER positive tumors are also progesterone receptor (PR) positive. A hormone receptor positive breast cancer grows much more slowly than hormone receptor negative tumors, and are much more likely to respond to hormone therapy with agents such as tamoxifen, an estrogen receptor antagonist, or aromatase inhibitors, which reduce the body’s natural estrogen production. (The role of progesterone and its receptors in breast cancer is complex and controversial; the addition of synthetic progestins to postmenopausal estrogen therapy has been consistently linked with increased risk of breast cancer, while estrogen alone or with natural progesterone has not.)

About 20% of breast cancers make excess amounts of the growth-promoting protein HER2/neu (usually called just HER2) and these cancers grow and spread more aggressively than cancers with a normal amount of HER2 protein. However, they are likely to respond to treatment with drugs that specifically target the HER2 protein, such as Herceptin (an immunotherapy that locks onto the HER2 protein and causes the immune system to attack the cancer cells) and Tykerb (a tyrosine kinase inhibitor that blocks the signals from HER2 telling the cells to divide and grow).

Triple-negative breast cancers, because they lack hormone receptors, grow and spread more quickly than other types of breast cancer and do not respond to hormone therapy, and while they lack the growth-promoting HER2 protein, they also cannot respond to HER2-targetting drugs like Herceptin. In these cases, chemotherapy is used for treatment even in early stages of the disease.

Who Is At Risk of Breast Cancer?

As women get older, their risk of developing breast cancer increases, as does the likelihood that the type of breast cancer is invasive. Some susceptibility to breast cancer is conferred by mutations in genes inherited from a parent, particularly in the BRCA1 and BRCA2 genes; heredity is thought to represent about 5-10% of breast cancer cases. Also, women who have already had a breast tumor are at a 3-4 fold increased risk of developing a new breast cancer either in the same or the other breast, which is not a recurrence of the original tumor.

Other risk factors for breast cancer include:

  • Higher lifetime exposure to endogenous estrogens, due to earlier onset of menstruation and/or later onset of menopause
  • Being overweight or obese
  • Drinking alcohol
  • Heavy smoking
  • Shift work, leading to reduced melatonin production (melatonin is protective against cancer)

What Can We Do About It?

While some risk factors are unavoidable, such as gender and age, much can be done through education, screening, and lifestyle adjustment to put women in control of their own risk and help avoid the more serious consequences of breast cancer.

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