Archive for the Breast Cancer category.
Posted on November 10th, 2007 by Canadian Health in
Breast Cancer There were about 186,000 new cases of breast cancer in the year 2000, it is the second leading cause of cancer death in women only superseded by lung cancer. There is an increased incidence probably because of the increased use of screening mammography, one in 10 women who live to the age of 80 will get breast cancer, not 1 in 10 women in this room, but 1 in 10 women that are able to live to the age of 80. We need to remember that 1% of all breast cancers do occur in men. Risk factors are well known. If you are over the age of 50, you have an increased risk of breast cancer just based on your age alone. If you have a personal history of breast cancer or a history of ovarian, uterine or colon cancer, you have an increased risk of breast cancer. Family history is classically the most important nonpersonal risk factor, the most important risk factor in a family is if it’s a maternal relative first degree premenopausal and breast cancer was bilateral. Adolescent exposure to radiation is becoming an increasingly common risk as children who were radiated in their teens, especially for Hodgkin’s disease or in older women for thyroid problem. It’s unclear whether exogenous estrogens or fertility drugs increase the risk of breast cancer unrelated to the other risk factors and this is still being debated in the literature.
The most common histology of breast cancer is an infiltrating ductal carcinoma which is approximately 90% of all breast cancers. The most common site is the upper outer quadrant and that’s only because there is more breast tissue in the upper outer quadrant than other parts of the breast. The most common metastases is to the axilla and about 1 to 2% of breast cancers are bilateral or occur in both breasts at the time of diagnosis. So when a woman presents with a palpable mass in one breast, we must remember not to forget the other side. Clinical presentations are by far and away now, an abnormal screening mammogram. A woman goes for her screening mammogram and something is found. The second most common presentation is a palpable mass, classically it’s new and classically it’s painless. About 1 to 2% of women who present with breast cancer have some associated pain or sensation so that should not be of note. But most breast cancers do not cause pain. Bloody nipple discharge is a rare presentation for breast cancer, the most common cause for bloody nipple discharge is an intraductal papilloma. Skin changes are a sign of advanced disease and occasionally a patient will present with axillary adenopathy alone and the breast cancer remains occult.
Sarcoma
Embryonal rhabdomyosarcomas (sarcoma botryoides) occurs almost exclusively in children younger than 5 years old. These children usually have vaginal bleeding or discharge, and grapelike, gray-red masses may protrude from the vagina.
Perioperative chemotherapy (vincristine, dactinomycin, cyclophosphamide) offers a survival advantage with various sarcomas. Thus, instead of exenteration, patients are probably best treated with preoperative combination chemotherapy, followed by tailored surgical management and the possibility of adjuvant radiation for patients with positive surgical margins.
In adults, leiomyosarcomas and mixed miillerian tumors are the most common tumors. As with similar sarcomas of other organs, mitotic counts are important in assessing malignant potential. Surgical excision of these tumor masses, with removal of adjacent organs, is the primary therapy. Adjuvant cisplatin with ifosfamide for mixed miillerian tumors and doxorubicin hydrochloride with or without cisplatin for leiomyosarcomas may prove effective. However, a large number of patients with vaginal sarcomas have not been treated with these agents.
Melanoma
About 150 cases of primary vaginal melanoma have been reported. The average age of patients is about 58, and patients present with bleeding, discharge, or a mass. Dark lesions of the vagina should be excised. These neoplasms most commonly occur in the lower anterior vaginal tube. Survival for this rare malignancy of the vascular vagina is poor: 5-10%.
Radical surgery (radical hysterectomy with radical vagi-nectomy or exenteration) may yield better 2-year survival rates than conservative therapy such as wide excision plus irradiation. Lymphadenectomy, directed against anatomic spread patterns, should be performed with radical surgery. Chemotherapy is of little value.
Use of Oral Contraceptives
Soon after the approval of oral contraceptives, a number of epidemiologic studies reported on the risk of breast cancer associated with them. Oral contraceptives are widely used, and any effect on the risk of breast cancer will have important public health implications. Studies suggest that, overall, there has been no increase in the risk of breast cancer for women who had ever used oral contraceptives; however, women who had used oral contraceptives for long periods were at higher risk of premenopausal breast cancer. This was noted among women who had used oral contraceptives before their first full-term pregnancy. It will be important to determine whether this finding in a subgroup of women using oral contraceptives is confirmed, and more important, whether the risk remains at advancing age.
Another study reexamined the data from the Cancer and Steroid Hormone Study to determine whether oral contraceptive use had different effects on the risk of breast cancer at different ages at diagnosis. Among women 20-34 years of age at diagnosis, those who had ever used oral contraceptives had a slightly higher risk of breast cancer than did women of the same ages who had never used oral contraceptives. The slightly increased risk in young women is compatible with the findings of other investigators. There appear to be no data to suggest changes in the prescribing practice for the use of oral contraceptives.
Dietary Fat Intake
International differences in rates of breast cancer and the striking increase among populations migrating from low-to high-incidence areas has suggested that environmental factors, possibly dietary, influence the occurrence of breast cancer. A number of studies addressing this issue have produced conflicting results and recommendations. In a recent study, no evidence was found of a positive association between total dietary fat intake and the risk of breast cancer. There was no reduction in risk, even among women whose energy intake from fat was less than 20% of the total energy intake. It appears unlikely that a reduction in total fat consumption by women in middle age and older will substantially reduce their risk of breast cancer.
Alcohol Consumption
A number of epidemiologic studies have shown a possible relationship between moderate drinking and breast cancer. However, the benefit of decreasing alcohol consumption, if any, needs to be evaluated by considering all the potential effects of alcohol on a woman’s overall risk profile. In that connection, data have also been published suggesting that among women, light to moderate alcohol consumption is associated with a reduced mortality rate. The apparent survival advantage is largely confined to women at greater risk for coronary heart disease.
Other Factors
Approximately 10% of patients with breast cancer have a history of trauma to the breast. This trauma probably results in increased attention to the breast and the discovery of a tumor or other changes that initiate breast self-examination.
Virus-like particles have been identified in human breast milk. There is no evidence, however, that viruses are involved in breast cancer risk.
A number of histologic changes have been noted in benign fibrocystic breasts, and some have been associated with the later development of breast cancer. The College of American Pathologists has published a consensus statement indicating that there is no increased risk for breast cancer in patients with conditions such as macrocysts or microcysts, duct ectasia, fibroadenoma, mild hyperplasia, mastitis, or squamous metaplasia. There is a slight increase in risk in patients with sclerosing adenosis; biopsy-proven hyperplasia that is moderate or florid, solid or papillary; and those who had papillomas with a fibrovascular core. Finally, risk increases substantially–fourfold to fivefold–in women with biopsy-proven atypical hyperplasia or a ductal or lobular carcinoma in situ.
Pathology
The histologic patterns of breast cancers can be divided into two types: 1) carcinomas of lobular epithelial original and 2) carcinomas of ductal epithelial origin. Carcinomas of lobular epithelial origin are generally classified on the basis of invasion: lobular cancer in situ or lobular neoplasia and invasive lobular cancer. In situ lobular carcinoma is almost always diagnosed as an incidental finding after the biopsy of a dominant mass or an occult lesion. The most important features of this lesion when planning treatment include bilaterality, multicentricity, and the relatively low rate of development of subsequent infiltrating carcinoma. If after biopsy the margins are clear, a reasonable treatment plan includes biannual physical examination and annual mammography. The alternative is to recommend mastectomy, usually bilateral.
In situ ductal carcinoma, if untreated, will develop in the ipsilateral breast in approximately 50% of cases. Standard treatment has been total mastectomy with or without conventional axillary dissection. Because of the advent of conservative techniques for small, invasive cancers, there has been considerable debate about conservative treatment for in situ ductal carcinoma. The most recent trial has suggested that appropriate treatment consists of wide local excision or segmental mastectomy followed by radiation therapy.
Reproductive History
Certain reproductive characteristics–nulliparity, early age of menarche, older age at menopause, and older age at first full-term pregnancy–have been associated with increased risk of breast cancer. Oophorectomy at an early age has been considered protective in reducing the risk of breast cancer in reproductive-age women by almost 70%. It has been suggested that the period between the onset of menses and the age of first pregnancy provides a “window of initiation” for the development of breast cancer. This theory presents a paradox, at least in terms of the functional activity of the breast. Anatomically and functionally the breasts undergo atrophy with advancing age. Less than 25% of breast cancers occur in premenopausal women.
It has been widely believed that lactation has no effect on the incidence or the risk of breast cancer. According to a recent study, however, there is a reduction in the risk of breast cancer among premenopausal women who have lactated, but no reduction among postmenopausal women with a history of lactation. Thus, the role of lactation, specifically the biologic effect of lactation on breast cells, is unclear. The stronger effect of lactation as a protective factor at an early age suggests that decreased exposure to ovarian hormones at a younger age may be important. This theory is in keeping with the previous discussion concerning early age of menarche and the effect of ovarian hormones on developing breast parenchyma. Lactation is a behavior that can be altered; although the apparent effect of lactation is not great, any reduction in breast cancer incidence would be significant, especially in younger women.
Estrogen Replacement Therapy
Physicians should understand the rationale for estrogen replacement therapy, especially in terms of the prevention of cardiovascular disease and osteoporosis, and at the same time be aware of the lack of data to support the unequivocal recommendations for estrogen replacement therapy in patients treated for breast cancer.
There are a number of interesting observations that suggest a relationship between estrogen replacement therapy and breast cancer. It has been known for many years that oophorectomy before the age of 35 years reduces the risk of breast cancer by 70%. Patients with metastatic breast cancer treated with aminoglutethimide, an aromatase inhibitor, have a marked reduction in estradiol from 15-20 pg/mL to about 5 pg/mL because of the failure of conversion of hormones into estrogen. The level of estradiol is increased to 30-35 pg/mL with estrogen replacement therapy.
A number of clinical studies have reported that the risk of breast cancer is slightly elevated among users of estrogen replacement therapy. A meta-analysis concluded that women who had used estrogen in the past are not at an increased risk, but that current use may be associated with increased risk, although the relationship to breast cancer mortality was less clear.
There is no question that breast cancer is related to reproductive events. Increasing attention to the contemporary preventive approach to breast cancer focuses on the physiologic effects of the sex steroid hormones and their possible interaction with family history. Adding to the potential risks of estrogen replacement therapy is that current use of estrogen replacement therapy may be associated with lower specificity and lower sensitivity of screening mammography.
Successful treatment of breast cancer depends on local control, and there is always the potential for distant metastasis. If the patient is free of metastatic disease, the question is moot. Unfortunately, not all of the patients with breast cancer are cured even with the most effective treatment. The effect of estrogen replacement therapy on occult metastatic disease is the basis for the caution regarding the use of estrogen replacement therapy in these patients. The receptor data and other prognostic factors appear to be of little value, at the present time at least, in deciding for or against estrogen replacement therapy in these patients. Although the original tumor may be estrogen receptor negative, the subsequent metastases may be estrogen receptor positive. Finally, it is important to understand that if overt metastatic disease is discovered, treatment–how-ever aggressive–will be ineffective.
In considering estrogen replacement therapy, therefore, the physician should discuss benefits and the risks with the patient, including the uncertainty of the available data regarding risk. Vaginal administration of estrogen is not without concern. Estrogen is absorbed readily from the vaginal mucosa, especially if it is atrophic. There is decreased absorption with increasing vaginal cornification, but the absorption is perhaps sufficient to stimulate occult micrometastases.
Epidemiology
The risk factors currently identified for breast cancer do not present a significant potential for control, nor are they as distinct as risk factors for lung cancer and cervical cancer. Other malignancies are associated with breast cancer, and multiple primary tumors of the ovary and uterus may be involved. Patients with endometrial cancer should be carefully screened with annual mammography; similarly, patients with breast cancer should be carefully observed for abnormal uterine bleeding.
Primary care physicians should be aware of a patient’s chances of developing breast cancer and the impact of breast cancer on the general public. Breast cancer is the most common cancer. The chance of developing breast cancer by age 25 is approximately 1 in 20,000; by the age of 60, it is 1 in 24. Another way of impressing this concept is that, in the absence of any major risk factors such as breast cancer in first-degree relatives, the chance of getting breast cancer between ages 30 and 40 is 1 in 1,000; between ages 40 and 50, it is 2 in 1,000; and between ages 50 and 60, it is 3 in 1,000.
Family History
The family history is an important factor in assessing an individual’s risk of a heritable predisposition to breast cancer. One should attempt to distinguish women carrying mutations in breast cancer susceptibility genes, in whom the risk of disease is very high, from women in those same families who have not inherited a susceptibility gene. The possibility of paternal transmission in affected families should be considered. Genetic studies suggest that a significant portion of familial breast cancer may be due to one or more dominantly inherited predisposing genes (see “Genetics and Gynecologic Cancer”).
The diagnosis and treatment of breast cancer have changed dramatically during the past two decades. Screening programs did not exist 25 years ago. The preferred treatment was radical mastectomy, and adjuvant therapy did not exist. This is in marked contrast to the current situation of well-organized screening programs, effective adjuvant therapy, and alternative treatment.
The most recent figures from the National Cancer Institute reveal that after a sharp rise in the percentage of women diagnosed with breast cancer from 1980 to 1987, there has been a decline in incidence, especially among women 50 years of age and older. The lifetime risk for developing breast cancer is one in nine. This reflects an increase in life expectancy of American women and the fact that breast cancer is a disease of older women. In addition, the increase is the result of the decision to include in the calculation women older than 85 years of age.
The American Cancer Society predicted 180,200 new cases of breast cancer and 43,900 deaths for 2006, representing 31% of all new cases of cancer and 17% of cancer deaths. The mortality rate for breast cancer has been unchanged since 1930, increasing on an average of 0.2% per year from 1973 to 1990, but decreasing in women under age 65 years by an average of 0.3% per year. Recent data, however, indicate that breast cancer mortality has decreased in whites by almost 5% from 1989 to 1992, probably as a result of an increase in the diagnosis of localized cancer and the increased use of adjuvant therapy and screening mammography.
The most important risk factor for breast cancer is advancing age. In women older than age 45 years, breast cancer occurs more frequently in upper socioeconomic classes, and whites are affected more than African Americans. Identified risk factors, either alone or in combination, explain only 21% of the risk among women age 30-54 years and 29% of the risk among women age 5584 years. Thus, from a practical standpoint, 80% of the women with breast cancer have none of the currently identified risk factors, and the clinician should assume that all women are at risk, particularly those older than 35 years of age.
Early detection is associated with increased survival and more cosmetic local treatment. Women should undergo screening and routine surveillance at timely intervals to assess risks and aid in early diagnosis. It is recommended that screening mammography be offered routinely every 1-2 years to women age 40-49 and annually to women older than age 50. Women age 35 and older with premenopausally diagnosed breast cancer in a first-degree relative also should be offered mammography.