breast cancer

Many women are concerned about risks of breast cancer, especially if they have a close relative who has had the disease. Here's some information, compiled from factsheets from the UK Cancer Research Campaign(date of publication: 1998)

There are large variations in the risk of breast cancer, both between countries where recorded incidence rates vary 30-fold, and also within countries over time. In addition, migration studies show an increase in risk when people migrate from low to high risk countries. Japanese migrants to the USA acquire incidence rates similar to the host population within two generations: the younger the migrant the sooner their risk approximates that of the host population. These observations suggest that genetic determinants of the disease are less important than environmental factors, and that prevention is possible. Although a number of risk factors have been linked to breast cancer, many relating to hormonal status, no major risk factor has been identified which can be used as a basis for primary prevention.

The strongest risk factor is age: the older the woman the higher the risk. Reproductive factors are linked to hormonal exposure: in general the greater the exposure to oestrogen, the higher the risk. Early age at menarche increases the risk and correlates with the international pattern of the disease. Low risk countries, such as China, have a later average age at menarche (17 years) compared to 12.8 in the USA. Late menopause after the age of 55 years approximately doubles the risk compared to menopause before the age of 45. An artificial menopause caused by bilateral oophorectomy before the age of 35 reduces the risk by two-thirds compared to women with a natural menopause (risk calculated before widespread administration of hormone replacement therapy (HRT)). Nulliparity and having a child after the age of 30 years approximately doubles the risk compared to a woman who has her first child before the age of 20. Age at menarche, age at menopause, parity and early pregnancy are well-established risk factors but it is not yet clear how these events affect a woman’s risk of developing breast cancer. Prenatal exposure to oestrogen is also under investigation.

A relatively small proportion of women, 5-10% of the population, are at increased risk due to an inherited susceptibility associated with a family history of breast and ovarian cancer, often occurring at young ages. The relative risk (RR) for a woman with one first degree relative (mother or sister) with breast cancer is raised slightly to between 1.5 and 2, and if two first degree relatives are affected the RR rises to between 4 and 6. The risk increases if the relative has bilateral disease and if the disease occurs at a young age: when both these conditions are fulfilled the cumulative probability of developing breast cancer may be as high as 40%.

Recently two breast cancer genes have been identified accounting for approximately 85% of families with four or more cases of breast cancer diagnosed under the age of 60 years. Both are large genes with many mutations. BRCA1 is a gene on the long arm of chromosome 17 and BRCA2 is on the long arm of chromosome 13. It is estimated that 2% of all breast cancers are due to BRCA1, 8% of breast cancers in women under 30 years and up to 20% of cases in Ashkenazi Jews who have breast cancer before the age of 40 years Other rare inherited conditions such as the Li-Fraumeni syndrome (associated with mutations in the p53 tumour suppressor gene on the short arm of chromosome 17), also increase the risk of breast cancer. In total around 5% of all breast cancer cases (around 1725 cases annually) may be caused by cancer predisposition genes. How best to identify, treat and counsel women at increased risk is currently being intensively investigated.

The heterogenous category known as benign breast disease carries only a slightly raised risk (RR 1.5) for malignant disease. However, for women within this category who have atypical hyperplasia, their risk is quadrupled (RR 4.0). Ninety percent of benign biopsy specimens do not show atypical hyperplasia. Cancer in the other breast also raises the risk four-fold, and both this and atypical hyper-plasia are associated with familial breast cancer.

The administration of artificial hormones in the form of oral contraceptives and HRT has also been studied. A recent meta-analysis of oral contraceptive studies concludes that there is a small increase in the risk of having breast cancer diagnosed during combined oral contraceptive use and in the following ten years, but the excess disappears ten years or more after cessation of use. The health benefits of HRT at present seem to outweigh the disadvantages, but some studies do show an increase in breast cancer risk after more than 10 years of use of unopposed oestrogen. Evaluation of the effects of oral contraceptives and HRT is continuing.

The effect of dietary factors on the aetiology of breast cancer is still unclear. Animal studies linking high fat diets with increased risk and international correlations between fat intake and breast cancer have not been confirmed by large prospective studies. There are many difficulties in measuring fat intake and it has been suggested that dietary fat intake during early life may be more important than during mid-life. Obesity in young women is associated with reduced risk.

Many of the risk factors detailed above will be difficult or impossible to change. However, there is evidence that certain forms of behaviour may protect against breast cancer, such as high levels of physical activity, breast feeding and diets high in fibre, fruit and vegetables.

For more information in the UK: leaflets are available from your GP, or local Well Woman clinic. Ask your GP for more specific personal risk assessment. Also see: tamoxifen.

If you're a man, please, please don't dismiss breast cancer as being something that only happens to women.

Breast cancers in men used to be extremely rare, and they're still uncommon. According to the American Cancer Society, in 1995 there were 1400 cases of breast cancer in U.S. males, and in 1998 there were about 1600.

The number of cases in men will likely continue to rise because of the amount of estrogenic pollutants people are being exposed to. Many plastics and pesticides mimic estrogen when they get in the human body, and they have been linked to breast cancer formation in both sexes.

Furthermore, men's breast cancers seem to be very aggressive and much more lethal than women's cancers. Medical researchers haven't yet determined whether this is because men put off going to the doctor until their cancers are advanced or because the cancers themselves are more invasive. Doctors do know that men who have naturally elevated estrogen levels (such as men with Kleinfelter's Syndrome) or who have a BRCA2 mutation are at a much higher risk. Men who are older, eat high-fat diets, or are overweight to the extent that they've developed excess breast tissue are also at higher risk, as are men who have pituitary or testicular function problems.

However, men of any age, size or condition can develop breast cancers and tumors. I dated a fellow in college who was rail-thin and athletic who developed a tumor under his nipple. He wouldn't have thought anything of the lump he felt one day in the shower, except that his mother had just had breast cancer surgery.

More recently, a close friend of mine was just diagnosed with breast cancer, but fortunately they caught it at a very early stage.

He, too, developed a tumor near his nipple. The first biopsy came back negative, but the tumor grew and became extremely painful, and he bugged his physician to have the thing taken out. No one but my friend was taking it very seriously, and his insurance company was balking at paying for his treatments, claiming it was "cosmetic surgery". But when they put him under the knife, the surgeon realized things looked wrong and they did a second biopsy in which the cancer was discovered.

The surgeon eventually had to take out 80% of the tissue in his right pectoral, plus the lymph nodes under his arm. The scar is deceptively small, just a half-moon incision following the curve of his nipple.

My friend is now undergoing radiation treatments with Cobalt 60. Five days a week, he goes down to the hospital for two hours. The radiation treatment itself only takes two minutes; the rest of it is getting prepped and waiting.

He's got runic markings on his chest to show the radiologist where to direct the beams; they gave him the option of having the markings inked in or tattooed on. He didn't want any more physical reminders of this illness than he's already got, so he opted for permanent marker. He has to cover the markings with waterproof tape when he takes a shower.

When he goes in the room, he lies on a table beneath the radiation machine. They lay a leaded mat like the ones you find at a dentist's office over the lower half of his body. They put a specially-fitted wire mesh mask over his face that they then affix to the table so that he can't move his head.

He says that the mask makes him claustrophobic. He'll get it as a souvenir when the treatments are done, and all the doctors and nurses will sign it.

Unfortunately, three days into his treatment he started to suffer from painful radiation burns on his chest. His doctor tells him that 25% of all patients get the burns as an unfortunate side effect. The burn covers most of his pectoral and looks like a cross between a moderate sunburn and a rash. More disturbingly, his scar looks roasted and bleeds from time to time. The doctors prescribed him a foul-smelling cream to rub on the burn, but that's it -- he's in for six more weeks of this.

The radiation treatments will also weaken him and probably destroy his appetite; the doctors have told him to eat high-calorie foods. Since he has high cholesterol, they've told him to try sports energy bars, peanuts, and raisins. He's going to lose a lot of weight, no matter what.

But all this is better than dying from the cancer. And his doctors say that as long as he completes his treatment, his chances for a cancer-free future are good.

So, whether you're male or female, pay attention to your body and examine yourself regularly. Please go see a doctor if you:

• detect a lump in your chest or breast
• have unusual discharge or seepage from your nipple
• have an ulcer or persistent rash on your nipple or skin
• have swelling in your armpit
• have unexplained pain in your pectoral or breast

This is gleaned from a telemedicine lecture from Virginia Mason in Seattle, Washington on October 19, 2009.

Screening for Breast Cancer in High Risk Women

In any woman alcohol does increase breast cancer risk, if there is more than two ounces intake daily. I tell people they can't save up for the weekend. 1.5 increase in relative risk. To put it in perspective, more than 2 ounces of alcohol is a risk equivalent to a first degree relative (mother, sister, daughter) with breast cancer.

Re MRI. There's a lot of battling going on at the research level about when to do an MRI for many reasons:

--high cost
--variable technique
--imperfect specificity
--patient barriers: size of patient/kidney function/claustrophobic
--questionable survival benefit

Virginia Mason (VM) has established a protocol for use of breast MRI. The recommendation for a breast MRI is that it be used for high risk patients as defined by:

--BRCA 1 & 2. Last year I learned that these are protective genes and it is their absence or mutation that causes the problem.
--> 20% risk (Gail model risk calculator)
--radiation to the chest age 10-30 (usually for another cancer)
--Li-Fraumeni (TP53 mutation) or Cowden (PTEN mutations)I had not heard of either of these genetic risks for breast cancer before. More on breast cancer genetics.

For high risk patients, MRIs should start at age 30, except for the inherited genetic problems, which should start at age 25 or 5-10 years younger than the youngest affected family member.

There is built in discrimination, in that MRI is so expensive, that only those with "good" insurance will get one. MRI is not being withheld from low risk patients: it really isn't helpful because they are not always easy to read and you can get false positives that lead to biopsies that make the person higher risk.....

Testing for BRCA 1 & 2 mutations is sometimes covered by insurance, and costs around $3700. My employer was changing insurance companies and the old one did cover $3200, while the new one didn't at all. I did the testing and paid $500. I have offered it to patients and have never had one agree; I found it hard to do and hard to go in for the results.

Studies are examining breast cancer genetics and mRNA expression of 16 genes. They have developed a recurrence score, divided in to low, medium and high. It gives an estimated breast cancer % recurrence over the next 10 years. 51% of node negative patients are low score and then do not need adjuvant therapy (such as tamoxifen, chemotherapy or radiation). People with high scores have a 27% recurrence rate over 10 years, so adjuvant therapy should be given. They are doing randomized trials of the intermediate scores -- either tamoxifen alone or tamoxifen and chemotherapy.

Tamoxifen is metabolized to endoxifen. However, 10% of patients are poor metabolizers. There is a Roche test of CYP2D6 (known as sip2-D-6) for $300 to identify poor metabolizers. Fluoxetine (prozac) and paroxetine (paxil) sometimes mess up the metabolism of tamoxifen by inhibiting CYP2D6 and shouldn't be used with it. Tamoxifen is being compared to other aromatase inhibitors. Hot flushes turn out to be important -- there are less in the tamoxifen non-metabolizers. Thus the doctor will be cheerful if the woman has hot flushes on tamoxifen, because they are likely to have a "better outcome". This is really getting in to "personalized medicine" where the genetics of an individual are guiding treatment. It is called molecular profiling.

There are arguments going on about whether the Gail Model high risk calculator is better than the genetic testing. Virginia Mason currently recommends doing genetic screening if the life expectancy is 5 years or less.

Inflammatory breast cancer requires an MRI. It turns out that inflammatory breast cancer cells can become sensitized to tamoxifen sometimes by estrogen. So even though we don't use hormones in people with breast cancer, there might be a small group where we do. It makes the cells hypersensitive to the tamoxifen.

That's what I got from the lecture. It is confusing, isn't it? Remember that we used to only diagnose stage III and IV breast cancer, so that is where the best studied treatments are. I have patients with early breast cancer who are offered 3-4 alternatives and want to know which is BEST. The truth is that it's all under study and is changing every year. I predict that there will be more and more genetic testing in the future, to direct treatment. I do worry that it will become impossibly expensive and complicated to treat even a hangnail. Doctors are in the unenviable position of being sued for doing too much OR too little. Let's all strive for perfection at all times.