Breast Cancer

The incidence of breast cancer has risen significantly in the US since the 1970’s. And although it is more common among women, it can also occur in men. Breast cancer is the most common cancer, the second most common cause of cancer death among women, and the third most common cause of cancer death overall behind lung and colon cancer in the US.

It is estimated that in 2007, nearly 41,000 people in the US will die of breast cancer. One out of eight women in the US have a chance of developing invasive breast cancer and a one in 33 will die from it. And according to the National Cancer Institute, about 1,700 men in the US learn they have breast cancer each year.

Different types of breast cancer, generally in order from most to least frequent, include:

• Ductal carcinoma
• Lobular carcinoma
• Inflammatory breast cancer
• Medullary carcinoma
• Colloid carcinoma
• Papillary carcinoma
• Metaplastic carcinoma

Although some cases of early breast cancer can be painful, breast cancer is usually discovered by feeling a breast lump or by a mammography before symptoms reveal themselves. The lump can be in the breast itself or persist above the collarbone or under the arm. Other potential symptoms include skin changes, breast discharge and nipple inversion.

Inflammatory breast cancer is particularly insidious in that in early stages it often escapes detection even by mammography or ultrasound. By the time symptoms appear, which are similar to those of a breast infection, the cancer has usually reached stage IIIb or IV. A summary of the stages of breast cancer follows:

• Stage 0 – cancer is localized and has not spread to nearby tissues
• Stage I – tumor is no larger than 2 cm. and no axillary lymph nodes (lymph nodes in the armpit) are involved
• Stage IIA – tumor is no larger than 2 cm. but axillary lymph nodes are involved, or tumor is 2-5 cm. but axillary nymph nodes are not involved
• Stage IIB – tumor is larger than 5 cm. but no axillary lymph nodes are involved, or tumor is 2-5 cm. but less than four axillary lymph nodes are involved
• Stage IIIA – tumor is larger than 5 cm. and axillary lymph nodes are involved, or tumor is 2-5 cm. and more than four axillary lymph nodes are involved
• Stage IIIB – tumor has penetrated the skin or chest wall and up to ten anxillary lymph nodes are involved
• Stage IIIC – tumor and more than ten anxillary lymph nodes are involved or at least one supraclavicular, infraclavicular, or internal mammary lymph node is involved
• Stage IV – systemic disease in which tumor has spread to distant organs and/or nymph nodes

All forms of cancer are thought to result from damaged DNA. But the mechanism behind how this happens remains unknown, although viral mutagenesis and exposure to ionizing radiation are among suspected culprits. Exposure to estrogens, among other factors, leads to an increased rate of mutation and decreased repair of mutated BRCA1, BRCA2 and p53 genes. But while the primary cause of breast cancer remains unknown, some secondary risk factors have been identified. They include:

• Hormones – sustained periods of increased blood levels of androstenedione, estrogen and testosterone have been linked with an increased risk of breast cancer. An early first menstrual period, late menopause, delaying the first childbirth, not breastfeeding, and not having children increase exposure to endogenous estrogens. As such, these circumstances are suspected of increasing the lifetime risk of developing breast cancer. On the other hand, increased levels of progesterone are associated with a decreased risk of developing breast cancer in pre-menopausal women. There may be a slight, short-term increase in the risk for breast cancer among women who use hormonal contraceptives.

There may or may not be a slight increase in breast cancer risk from the use of short-term hormonal treatment for menopausal symptoms. But while the link of the long-term use of hormone replacement therapy (HRT) with significant increases in the risk for breast cancer has been widely publicized, the increase in risk starts to become evident within a year or two of starting HRT. This is the case for oestrogen-only HRT, and even more so for combined oestrogen-progestogen HRT. There are other risks associated with HRT, and these should be weighed carefully against HRT’s benefits before commencing such forms of treatment.

• Diet – low fat diets may decrease the chance of getting breast cancer or its recurrence.
• Obesity – weight gain after menopause can increase a woman’s risk for breast cancer. A recent study found that a 22 pound increase in weight after menopause increases the chance of developing breast cancer by 18 percent.
• Gaining weight after the menopause can increase a woman’s risk. A recent study found that putting on 9.9kg (22lbs) after menopause increased the risk of developing breast cancer by 18%.
• Age – the probability of breast cancer not only increases with age, it tends to become more aggressive than in younger people. One notable exception is that of inflammatory breast cancer discussed above. Inflammatory breast cancer disproportionately occurs in younger people.
• Alcohol – while alcohol generally appears to increase the risk of breast cancer, studies are not consistent. The National Cancer Institute has reported that two drinks a day can increase the risk of breast cancer by about 25 percent. Another study suggests that women who drink red wine frequently may have an increased risk of developing breast cancer. Other studies suggest that consumption of Vitamin B9 (folic acid), such as that found in citrus fruits, dark green leafy vegetables, peas and dried beans, counteracts the breast cancer risk associated with alcohol intake.
• Environmental – studies are also not consistent on how much, or even whether active smoking or secondhand smoke increase the risk of breast cancer. In addition to diet, radiation and pharmaceuticals, however, there is a growing body of evidence that exposure to certain toxic chemicals and compounds that mimic hormones contribute to the development of breast cancer. Such compounds include cosmetics, cleaning products, and chemicals used in pesticides.
• According to Robbins & Cotran Pathologic Basis of Disease, those in families with mutations in the BRCA1 and BRCA2 genes have a 60 to 80 percent risk of developing breast cancer. A woman whose mother or sister has been diagnosed with breast cancer is twice as likely to get breast cancer than a woman without a familial history. Overall, there is a strong inherited familial risk in about five percent of breast cancer cases.
• Light levels – the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute recently concluded a study suggesting that exposure to artificial light at night might be a factor for breast cancer.

A legal BLOG addressing the rights of women who have developed breast cancer after HRT therapy can be found at http://www.the-injury-lawyer-directory.com/hormone.html.

Many toxic chemicals and other environmental factors have been credibly linked to chronic diseases including breast cancer. The Breast Cancer Fund has recommended the following environmental prevention methods, among others:

• Choose chlorine-free paper products.
• Choose hormone-free meats and dairy products and pesticide-free organic produce.
• Select less expensive household cleaners such as baking soda, vinegar and borax soap over those that contain bleach.
• Seek alternatives to chemical bug and weed killers.
• Avoid polyvinyl chloride (PVC) plastic products since they release carcinogens into the water and air during their manufacture.
• Do not allow children to put toys made from PVC into their mouths.
• Do not place plastic or plastic wrap in the microwave since this may release hormone-disrupting chemicals called phthalates into foods and beverages.
• Avoid breathing in secondhand tobacco smoke since it contains polycyclic aromatic hydrocarbons (PAHs), which are linked to breast cancer. Secondhand smoke, in fact, can increase the risk of breast cancer more than active smoking.
• Be an advocate for cleaner air. Fumes and soot released by automobiles, diesel trucks and factories also contain PAHs.
• Minimize your exposure to X-rays, CT scans and even Mammograms. While screening through Mammograms may benefit postmenopausal women, mammography is controversial for women in their 30s and 40s. When getting an X-ray, request protection with a lead shield for areas of your body not being X-rayed. Be aware that the effects of radiation are cumulative, which means that multiple low doses could be as harmful as a single high dose.
• Explore alternatives to artificial estrogens (see Hormones as a secondary risk factor above)
• Choose cosmetics that do not contain chemicals linked to cancer, birth defects, infertility and brain damage

Women at high risk of breast cancer may wish to consider removal of their ovaries (prophylactic oophorectomy) post-child-bearing. This can reduce the risk for developing breast cancer by 60 percent as well as for ovarian cancer by 96 percent.

While regular breast self-examinations are encouraged, mammography can generally detect cancers that are smaller than those detected clinically and remains the screening method of choice. Mammography has been demonstrated to reduce breast cancer-related deaths by 20-30 percent.

The National Cancer Institute recommends a baseline mammogram at age 35, mammograms every other year starting at age 40, and annual mammograms starting at age 50. Women with one or more first-degree relatives who’ve had pre-menopausal breast cancer should begin screening earlier. It is generally recommended that screening begin ten years earlier than the age at which the relative was diagnosed.

Magnetic resonance imaging (MRI) scans can detect cancers not visible on mammograms. But because they are less specific, they can result with up to five percent false positives that can create psychological hardships. They are also relatively expensive and require the intravenous injection of a contrast agent. MRI’s may be indicated for women with:

• Strong family history of breast cancer
• BRCA-1 or BRCA-2 oncogene mutations
• Breast implants
• A history of previous breast biopsy surgeries or lumpectomy
• An unknown primary tumor with axillary metastasis
• Scarred or very dense breast tissue

Ultrasound on its own is not an adequate screening tool. It can be useful, however, for directing image-guided biopsies and characterizing palpable tumors.

Procedures such as fine-needle aspiration, ductal lavage, nipple aspirates, and core needle biopsy have been devised to collect tissue for pathological examination prior to surgery. But these procedures have limitations since they sometimes do not yield enough tissue or miss the cancer. A diagnosis is therefore usually not established until after tissue is obtained at the time of surgical treatment.

Imaging tests including chest x-rays, MRIs, bone scans, CTs, and PET scans are used to detect if the cancer has spread from its primary tumor. Breast lesions and tumors are also tested for markers that can be used to follow up disease activity and to help select effective drugs for treatment.

Treatments for breast cancer currently used are termed standard treatments. Newer treatments are being tested in clinical trials and patients may wish to consider participating. Information about ongoing clinical trials is available at the National Cancer Institute website.

Treatment will vary depending on the type and stage of breast cancer the patient is in. Generally, four types of standard treatment are used:

Surgery to remove the cancer from the breast is the most widely used type of treatment. Different kinds of surgery include:

• Lumpectomy – removal of the lump or tumor and a small amount of surrounding tissue
• Partial or segmental mastectomy – removal of part of the breast that has cancer and some of the surrounding tissue
• Total or simple mastectomy – the entire breast is removed. Some axillary lymph nodes (lymph nodes under the arm) may be removed for biopsy, usually through a separate incision
• Modified radical mastectomy – removal of the breast, many of the axillary lymph nodes, the lining over the chest muscles and, if needed, part of the chest wall muscles
• Radical or Halsted radical mastectomy – removal of the breast, chest wall muscles under the breast, and all axillary lymph nodes.

Lumpectomy and partial mastectomy are known as breast-conserving surgeries. In breast-conserving surgery, some axillary lymph nodes may also be removed for biopsy. Patients who undergo mastectomy may consider breast reconstruction in which the patient’s own non-breast tissue or implants are used to rebuild a breast shape.

But even if all the cancer seen at the time of surgery is removed, adjuvant therapy, or radiation, chemotherapy, or hormone therapy is given to increase the chances any cancer cells that may be left after surgery are killed.

Radiation therapy uses high-energy x-rays or other kinds of radiation to kill cancer cells or stop their growth. Depending on the stage and type of the breast cancer being treated, internal or external radiation therapy is used. In internal radiation therapy a radioactive substance is sealed in needles, wires, seeds, or catheters and placed near or directly into the cancer. In external radiation therapy a machine is used to send radiation toward the cancer.

Chemotherapy uses drugs to kill cancer cells or prevent them from dividing. Again, depending on the stage and type of the breast cancer being treated, either regional or systemic chemotherapy will be used. In regional chemotherapy, the drug(s) are introduced directly into an organ, body cavity, or the spinal column. In Systemic chemotherapy, the drugs enter the blood stream after being swallowed or injected.

There are tests that can show whether the cancer cells have receptors, or places where hormones can attach and cause the cancer to grow. Hormone therapy is designed to remove or block the action of these hormones. Hormone therapy with an aromatase inhibitor prevents androgen from converting to estrogen, which hormone-dependent breast cancers in some postmenopausal women needs to grow. Hormone therapy with estrogens or tamoxifen can act on cells throughout the body, but can increase the risk for developing endometrial cancer. Women taking tamoxifen should therefore immediately report any vaginal bleeding other than menstrual, and have an annual pelvic exam.

New types of treatment being tested in clinical trials include surgery after sentinel lymph node biopsy, high-dose chemotherapy with stem cell transplant, and monoclonal antibody adjuvant therapy.

Early detection and new treatments have increased the survival rate of women diagnosed with breast cancer. The 5-year survival rate is 80 percent and 88 percent of women diagnosed with breast cancer can expect to survive more than ten years. Unfortunately, women in lower economic and social groups continue to have comparatively lower survival rates. Survival rates can also be affected by some of the following factors:

• The location of the tumor and how far it has spread – 5-year survival rates for those with ductal carcinoma that has not spread to the lymph nodes is up to 98 percent. But even in these cases, the recurrence rate is 9-30 percent. If the tumor is larger than 5cm. or has spread to several nymph nodes, the survival rate drops to 75 percent or lower. If the cancer spreads to other sites, patients treated with chemotherapy are expected to live one to two years, although many live much longer. Tumors that develop toward the outside of the breast have a better prognosis than those that occur more toward the middle.
• Whether the tumor is hormone receptor positive or negative – women with receptor-positive cells have a better prognosis because these types of cells grow more slowly and more treatment options are available to combat them. Hormone receptor-negative cells usually require chemotherapy.
• Genetic factors – while women with inherited BRCA1 or BRCA2 mutations have a higher risk for developing cancer, it is not clear how these mutations may affect their prognosis other than that tumors that develop in these women tend to be hormone receptor negative.
• Tumor size and shape – large tumors and undifferentiated tumors with less distinct margins tend to be more dangerous.
• Rate of cell division – rapidly growing tumors are more dangerous. There are several tests that measure different aspects of cancer cell division. The mitotic index (MI), for instance, measures the rate at which cells divide. Other tests measure cells at certain phases of their division.
• Biologic markers – numerous substances in cancer cells that may indicate a cancer’s likelihood of spreading are being investigated. These chemical markers may help doctors in selecting effective treatments and could help with the development of new drugs.

While women who develop breast cancer have a higher risk of developing cancer in the other breast, the outlook for the new cancer is independent from those of the first one. Any recurrence will usually occur within five years of treatment although 25 percent of recurrences take place after this time.