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Diagnosis and Treatment of Breast Cancer

Breast cancer is the most common diagnosed cancer in women. Itís not the most common cause of cancer death in women. That goes to lung cancer which occurs much less frequently than breast cancer but the morbidity is a great deal higher. These numbers have remained fairly stable over time. The mortality has also brest cancer, breast cancer, breast canser, best cancer

There are a number of risk factors that have been noted for breast cancer. The greatest risk factor is probably age and the peak incidence of breast cancer occurs between the fifth and sixth decade. If youíve had a previous history of breast cancer in one breast, youíre certainly at increased risk to develop a second breast cancer either in the breast thatís had lumpectomy and radiation or in the other breast. Family history clearly puts you at some risk and

Of course, now there are genes that weíve identified that are inherited in an autosomal dominant way that confer lifetime risk in the 80% range and these are BRAC-1 and BRAC-2 genes. Other genes that are associated with breast cancers, P53, abnormality in the P53 gene and the 

Lifestyle is becoming increasingly recognized as having risk for breast cancer and smoking and alcohol intake has been related to an increased risk. Now there are a couple of studies that show vigorous exercise, particularly in the teenage years, may 

As I noted there are four cloned genes that we know about that predispose to breast cancer. All of these conferring risk in an autosomally dominant way: BRAC-1, BRAC-2 Ė these are the breast and ovarian syndromes, ataxia telangiectasia. If the patients are homozygous, they donít live to a very long life but if theyíre heterozygous, they

Well, what is the standard screening for breast cancer? Certainly self exam, I think, should be incorporated although sometimes people argue whether studies show that this is useful. The clinical physical exam is of use and the main imaging technique for screening is mammogram. Breast self-exam in a couple of old prospective studies has shown

These are the American Cancer Society guidelines for early detection of breast cancer and the NIH has come more into line now with these guidelines. A few years ago they were not so aligned but from age 20-39, clinical breast exam by a physician or nurse every three years and a monthly breast self exam. Age 40 or older, and this is the difference, annual mammography, annual clinical breast exam and monthly breast self exam. Prior to this, the NIH had not recommended mammograms until

Ductal carcinoma in situ. This is a very controversial area in terms of management. The choices, I think, are mainly mastectomy with no axillary dissection. This is only in those cases where there is no invasive disease noted versus a lumpectomy and radiation versus a lumpectomy with no other therapy. Thereís a randomized trial really looking at these three various options and the lumpectomy alone had an increased incidence of local recurrence. There are certainly places like 

Lobular carcinoma in situ I look at as just a marker for risk not much unlike family history or other risk factors and I think that diagnosis warrants closer surveillance. Only in those patients who have other high risk or have breasts that

This is a look at mastectomy versus lumpectomy radiation and axillary dissection. This is at eight year followup. The earliest publication with followup is now at 20 years. Similar studies have reproduced these exact results in Europe

There are a few reasons not to do a lumpectomy and radiation. If youíve got a very large tumor in a small breast, youíre not going to get a very good cosmetic result and it probably isnít the right thing to do. If thereís a multifocal tumor throughout the breast, doing lumpectomy is not really feasible. If the breast is very dense, a lot of other

If you have metastatic disease, then that makes you an M1. So itís either you have metastatic disease or you donít. Then you put these T and M classifications together. Thereís only one way to be a Stage I breast cancer and thatís to have a tumor less than 2 cm, a T1 lesion, no nodes and no metastases. Anytime you have metastases, no matter what your T or your N, youíre a Stage IV.

Stage II can be all kinds of things and itís easier to remember that Stage II is anything thatís not Stage I, III or IV. Stage III disease is anytime you have a T4 lesion, youíre going to be a Stage III. Letís look at Stage III. Any T4 will put you in a Stage III. Any T3 with positive nodes is going to make you a Stage III. Any N2 disease will make you a Stage III and all the rest will be a Stage II. So the minute you have positive nodes, it makes you in Stage II or III. If itís not N2 disease and itís not a T4 lesion and itís not a T3 lesion, youíll be a Stage II.

If you go back and look at it, it makes a lot of sense. The only way you can be a T3 and still be a Stage II is not to have any positive nodes and that doesnít happen very often. So all the T1 and N1 combinations make you a Stage II. Anytime you have nodes that arenít N2 disease, youíll end up being a Stage II usually.

Well, we use all these risk factors to decide who we think needs systemic therapy to try to eradicate microscopic disease and hopefully change that person from going on and relapsing from breast cancer to being cured of breast cancer. Clearly, when you saw a Stage II line that dropped right to 50%, all those patients are at high risk for relapse

The choices for systemic adjuvant therapy, for estrogen receptor and progesterone receptor positive patients who are postmenopausal, hormone therapy can be as effective an adjuvant therapy as combination chemotherapy. For ER negative patients, combination chemotherapy is superior to hormone therapy and for all premenopausal women, regardless of their ER/PR status, combination chemotherapy is superior to hormone therapy. But hormone therapy

Hormone therapy is useful for estrogen receptor positive postmenopausal women and my bent, and I think this is increasingly popular, is those women at low risk. So postmenopausal women, even if theyíre ER positive with a number of positive nodes or other high risk factors, you may consider giving them chemotherapy then followed by hormone therapy. Premenopausal women who are ER positive would also be considered for chemotherapy then followed by tamoxifen. I donít use tamoxifen and chemotherapy together and I donít think most people do. It does

This looks at patients given different doses of Cytoxan and Adriamycin 5-FU and this solid line, in terms of disease free survival and overall survival are those patients who are more aggressively dosed than patients who are given a lower dose. Dose does matter. Dose over time or dose intensity is a predictor for outcome.

These look at HUR2-nu expression and if you overexpress HUR2-nu, those patients who were HUR2 negative, they seem to fair pretty well whether they got high doses of chemotherapy or low doses of chemotherapy. But if you were going to get cured, you had to get high doses of chemotherapy if you overexpressed HUR2-nu. So I think HUR2-nu is a predictor for outcome. It also tells you how you have to treat patients. Thereís also increasing information that hormone therapy is not useful for patients who overexpress HUR2-nu or their tumors overexpress HUR2-nu and that CMF probably isnít very useful and that you need to use Adriamycin in

What are the short term side effects from chemotherapy? Clearly alopecia in most of the regimens used. Weight gain is very common. This always comes as a shock to patients. Fatigue is the overwhelming most common and

Of more concern are the long term side effects from adjuvant chemotherapy particularly if youíre treating young women. It can cause premature menopause and then these women have usually not been thought to be eligible for

Tamoxifen needs to be used at least more than two years and probably for five years and probably not for more than five years. At more than five years, there may actually be an ability for tumor cells to learn to use tamoxifen to grow

Tamoxifen, and you probably have heard so much about tamoxifen in the last few weeks you canít stand it, probably benefits bone density and blood lipids. In the trial for prevention of breast cancer in normal women, they couldnít really show that but with only four years followup I donít think thatís so surprising and I think with longer followup they may be able to demonstrate that. But clearly in breast cancer patients weíve known for a long time it reduces the risk of contralateral breast cancers by 50%. I think it reduces the risk of new breast cancers in the lumpectomy radiated breast and now we know that in women at risk for breast cancer who have not had breast cancer, tamoxifen reduces the risk of 

What is the role of adjuvant radiation? I think the thinking about this has changed quite a bit in the past few months. I used to say that local radiation therapy only prevented relapse in the local area and didnít do anything much for overall survival. Thereís two very impressive articles in the New England Journal in October of last year and it showed that patients with any positive nodes receiving radiation therapy had a better survival when that was combined with chemotherapy versus chemotherapy alone. Most of the chemotherapy was with cytoxan methotrexate 5FU. Even in patients who had few nodes, one to three positive nodes, these are the patients who got radiation and