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Not all breast cancers behave the same

Philadelphia Inquirer (PA)


Oct. 06--The pink-laden ads of October refer to a single, straightforward disease called "breast cancer."

In reality, there are distinct types and classifications, based on where the cancer began, how it looks under the microscope, and whether it is still confined to its starting place.

Breast cancers are further categorized based on whether the malignancy is fueled by hormones, and by the newest measurable characteristic -- molecular activity.

The four major molecular subtypes, which are determined by gene-expression profiling, are still largely a research tool. But they are increasingly being used to predict patients' responses and select the best combinations of surgery, radiation, chemotherapy, hormonal drugs, and molecularly targeted therapy.

"We used to think of cancer just as the histology [appearance] and origination of the cells," said Richard Bleicher, a surgical oncologist at Fox Chase Cancer Center. "What we've found, though, is that they can better be grouped by genomic subtypes -- groups of cancers that have similar responses and outcomes."

Marisa Weiss, a Narberth breast cancer oncologist and president of the online resource, said: "What we're now trying to do is understand the personality of the cancer -- what makes it tick, what are the genes and proteins that are running the cell."

Here is an overview of breast cancer classifications, based on information from the National Cancer Insitute, the American Cancer Society,, Fox Chase, and the Mayo Clinic.

Pre-invasive cancer

Ductal carcinoma in situ (DCIS) is so named because the abnormal cells are still in place ("in situ") in the milk ducts where they arose. Thanks to early detection with mammography, about 60,000 cases of DCIS -- 1 out of 5 new breast cancers -- are diagnosed annually in the United States. On mammograms, DCIS may appear as white specks called microcalcifications.

There is no sure way to tell whether DCIS will develop the ability to invade surrounding tissue, so surgery, and usually radiation, is recommended.

Lobular carcinoma in situ, also called lobular neoplasia, is confined to the milk-producing glands. Only a few women per 100,000 develop LCIS. It is usually invisible on mammograms and detected during a biopsy done for another reason. LCIS is usually not treated with surgery, but because it raises invasive cancer risk, the risk-reducing drug tamoxifen is recommended.

Tissue of origin

Invasive ductal carcinoma, which begins in the milk ducts, accounts for 80 percent of all breast cancers. Rare subtypes of invasive ductal cancer are named for how the cells look under a microscope -- their shape or arrangement. These subtypes generally have a good prognosis, although they may be present with other, more aggressive types.

Invasive lobular carcinoma, which accounts for about 10 percent of invasive cancers, begins in the milk-producing lobules. Unlike ductal cancer cells, which tend to form a mass that may be felt as a lump, lobular cancer cells invade in a line, creating a web. This is difficult to detect by feeling or mammography, so the tumor may be large by the time it causes noticeable symptoms, such as pulling of the skin or nipple.

In rare cases, cancer begins in connective breast tissue -- muscles, fat, or blood vessels. Examples include Phyllodes tumor and angiosarcoma. Paget's Disease is a rare cancer of the nipple and areola.

Inflammatory breast cancer

This very aggressive ductal cancer, named for the breast reddening and swelling that are early symptoms, accounts for fewer than 5 percent of all breast cancers, but is more common among African American women. Typically, inflammatory tumors are not fueled by estrogen and progesterone, so hormone therapies such as tamoxifen are not effective. Intensive multimodal treatment, including chemotherapy before and after surgery, is standard.

Hormone status

In addition to the classifications above, cancers can be analyzed for their sensitivity to the body's sex hormones. Estrogen receptor-positive and progesterone receptor-positive tumors can be treated with hormone-blocking medications such as tamoxifen and aromatase inhibitors.

Molecular subtypes

Luminal A cancers are hormone-receptor positive, and HER-2 negative -- meaning they lack a gene mutation that causes overproduction of the cell-growth receptor HER-2. HER-2 positive cancers are aggressive but respond to the targeted drug Herceptin.

Luminal B cancers are positive for estrogen, progesterone, and HER-2 receptors.

Basal-like cancers, also called triple negative, are negative for hormone receptors and HER-2 receptors, making them particularly tough to treat. Intensive chemotherapy is standard.




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