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Biomedical subjects

I C Henderson

Publications and source records attributed to I C Henderson.

At least 19 recordsLinked to original sources
PubMed1992

Biologic variations of tumors.

Few tumors are so heterogeneous in their growth rates and patterns of metastasis as breast cancer. In general, the clinical phase of this disease is much longer than that of most other tumors. It is assumed that the preclinical phase is similarly long and this is one reason that the use of screening mammography has reduced breast cancer mortality. Mammography is not equally effective in all patient populations, but it has not yet been possible to precisely define those populations of women more or less likely to benefit from periodic mammography. Future studies should place greater emphasis on the correlation between frequency of mammography and biologic variations.

Age Factors↗
PubMed1992

Carotenoids, retinol, and vitamin E and risk of proliferative benign breast disease and breast cancer.

We investigated the relationship between serum levels of retinol, beta-carotene, alpha-carotene, lycopene, alpha-tocopherol, and gamma-tocopherol as well as intakes of retinol, carotene, and vitamin E and the risks of breast cancer and proliferative benign breast disease (BBD) in a case-control study of postmenopausal women in the Boston, MA (United States) area. Serum nutrient data were available for 377 women with newly diagnosed stage I or II breast cancer and 173 women with proliferative BBD. Controls were 403 women who were evaluated at the same institutions but did not require a breast biopsy or whose biopsy revealed nonproliferative BBD. We observed no significant associations between serum levels of these micronutrients and risk of proliferative BBD or breast cancer. The risk of breast cancer was decreased among women in the highest quintile of intake of vitamin E from food sources only (odds ratio [OR] for the highest quintile = 0.4, 95 percent confidence interval [CI] = 0.2-0.9; P, trend across quintiles = 0.02) but less so for total vitamin E intake including supplements (OR = 0.7, CI = 0.4-1.3; P, trend = 0.07).

Aged↗
PubMed1992

Systemic adjuvant therapy for breast cancer.

Systemic therapy for operable breast cancer can delay the time to recurrence. Recurrence of breast cancer can follow a variable clinical course but will lead to death in virtually all cases. This delay is reflected in an accompanying improvement in overall survival with treatment. Almost 35 years have passed since the introduction of adjuvant chemotherapy, whereas adjuvant tamoxifen trials were begun 17 years ago. In that time, only in a minority of patients has a clear consensus emerged on the appropriate use of adjuvant therapies. Overview analysis from large numbers of controlled clinical trials has produced a much larger data base for examining the effects of hormonal and cytotoxic therapy on the outcome of patients with early-stage breast cancer and provides greater statistical power to detect small differences in particular subgroups of patients, which may not have been apparent in individual studies. Patients with involved lymph nodes are now routinely treated with chemotherapy if they are premenopausal and with tamoxifen if they are postmenopausal, especially if their tumors contain estrogen receptor. More recent trials attempt to examine the use of these therapies outside of these prescribed groups as well as the introduction of new chemotherapeutic agents and dosage regimens, some of which are based on biologic principles of alternating, non-cross-resistant therapy and dose responsiveness. Treatment of node-negative breast cancer remains controversial. Small but real differences in odds of relapse have emerged with adjuvant treatment, although the nature of the risks and benefits remains to be defined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cytosine arabinoside and cisplatin for advanced breast cancer. A phase II study of the Cancer and Leukemia Group B.

Forty-four women with advanced breast cancer participated in a prospective clinical trial to evaluate the efficacy and toxicity of a regimen consisting of cytosine arabinoside and cisplatin. All patients had previously received chemotherapy. Three patients (7%) responded to therapy with response durations of 153, 160, and 441 days. The median time to disease progression and median survival time in all 44 patients were 2.3 and 5 months, respectively. This regimen had significant toxicity, with most patients experiencing severe or life-threatening hematologic, renal, or infectious complications. This regimen cannot be recommended for previously treated patients with advanced breast cancer.

Adult↗
PubMed1991

Window of opportunity.

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Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Phase II study of echinomycin in patients with advanced breast cancer: a report of Cancer and Leukemia Group B protocol 8641.

Twenty-five women with advanced histologically documented stage IV recurrent or inoperable breast cancer were enrolled on a phase II study of echinomycin administered at a dose of 1.2 mg/m2 intravenously over 30 minutes weekly for 4 weeks followed by a two week rest period. Seventy-six percent of patients had visceral dominant disease at study entry and all patients had previously received chemotherapy. One of 21 eligible patients had a partial response lasting 147 days. The median survival for this group of patients was 5.9 months and the median time to treatment failure was 1.7 months. Nausea and vomiting was the primary toxic effect and was severe or life-threatening in 43% of patients. Transient elevation of liver enzymes occurred in 30% of patients. Bone marrow suppression was not significant. Echinomycin as employed in this study did not demonstrate significant antitumor activity in previously treated patients with advanced breast cancer.

Adenocarcinoma↗
PubMed1991

Specificity of low dose fadrozole hydrochloride (CGS 16949A) as an aromatase inhibitor.

CGS 16949A (fadrozole hydrochloride), a potent cytochrome P450-mediated steroidogenesis inhibitor, blocks aromatase at low doses, but other biosynthetic steps at higher concentrations. Recent studies demonstrated inhibition of C11-hydroxylase, corticosterone methyloxidase-II, and deoxycorticosterone to corticosterone conversion with this agent at some-what higher concentrations than those required for blockade of aromatase. Based upon phase I studies, we postulated that relatively selective inhibition of aromatase might be possible if sufficiently low doses of CGS 16949A were used. A phase II study in 54 postmenopausal women with metastatic breast cancer examined the effects of low dose CGS 16949A on estrogen, mineralocorticoid, and glucocorticoid secretion. Two dose schedules and two dose levels were chosen based upon our prior dose escalation protocol study. Plasma estrone, estradiol, and estrone sulfate as well as urinary estrone and estradiol fell equally with 1.8-4 mg CGS 16949A given either on a twice daily or three times daily dose schedule. Isotopic kinetic studies demonstrated an 84% decrease in the rate of conversion of androstenedione to estrone to 0.40 +/- 0.07% (patients receiving 1.8-4 mg CGS 16949A daily). With these three regimens, basal levels of aldosterone and cortisol did not change significantly over a 12-week period of observation. Clinical examination, plasma electrolytes, and urinary sodium/potassium ratios suggested no biological evidence of mineralo-corticoid deficiency. ACTH-stimulated cortisol concentrations, however, were blunted at each dose level compared to pretreatment values. Nonetheless, peak responses exceeded 550 nmol/L, or a basal to peak difference of 190 nmol/L or greater, in 97% of instances. This probably reflected inhibition of C11-hydroxylase, since basal and ACTH-stimulated levels of 11-deoxycortisol were increased in response to CGS 16949A. Androstenedione and 17 alpha-hydroxyprogesterone also exhibited an upward trend in response to drug treatment. ACTH-stimulated aldosterone levels were blunted to a greater extent than those of cortisol, probably as a reflection of corticosterone methyloxidase type II blockade. Overall, the results suggest that CGS 16949A, at doses of 1.8-2 mg daily, blocks aromatase effectively and does not produce clinically important inhibition of cortisol or aldosterone biosynthesis. Thus, this agent can probably be used safely without glucocorticoid or mineralocorticoid supplementation.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Conservative surgery and radiotherapy for early breast cancer.

In 1984, as part of a prior American Cancer Society National Conference on Breast Cancer, the authors reported on the status of conservative surgery (CS) and radiotherapy (RT) as primary local treatment for women with early stage breast cancer. Since that time, additional data have become available regarding the use of this approach and its comparability to mastectomy. In general, these data support the use of CS and RT and, as a result, this approach is now more widely employed in the United States and abroad than it was in 1984. The current focus of inquiry has shifted from whether or not CS and RT is an acceptable option for patients with early stage breast cancer to the following questions. For which patients are CS and RT suitable? What are the best techniques of surgery and RT? Are there any patients who can be treated safely with CS without RT? How should RT and systemic therapy be integrated when both are to be used? In this report, recent results on the use of CS and RT from both retrospective and prospective trials are summarized, and these current areas of inquiry are addressed.

Breast Neoplasms↗
PubMed1990

Comprehensive management of disseminated breast cancer.

The management of patients with metastatic breast cancer is best achieved by the judicious use of local and systemic measures that palliate symptoms and improve overall quality of life. When two treatment approaches are known to be equally efficacious, the less toxic should be used. When disease is limited to one or two sites and the patient has an indolent form of the disease, the patient's symptoms are often best palliated with the use of surgery or radiotherapy alone. When multiple sites of disease are evident or the disease is progressing more rapidly, systemic therapy is preferred, and local therapies should be added when the patient is clearly refractory to systemic therapy or when the disease site is unlikely to be adequately palliated with systemic therapy. The use of any of these therapies, including chemotherapy, has a relatively small effect on the median survival of patients with metastatic breast cancer. However, improvements in quality of life are usually greatest with regimens inducing the highest response rates, even when these regimens are associated with greater toxicity. The characteristics of patients likely to respond to endocrine therapy are well defined; in these patients endocrine therapy should be used as the first form of systemic therapy. Among endocrine therapies, the least toxic is used first. The selection of patients for chemotherapy is largely a process of exclusion. When chemotherapy is used, there are a number of different strategies for sequencing chemotherapy that appear to be equally efficacious. In general, patients should be treated with standard doses of drug combinations for a period in excess of 3 months. When used inappropriately, especially in asymptomatic patients, these therapies may actually compromise the patient's quality of life. The use of surgery, radiation therapy, and systemic therapy should be integrated with various types of psychosupport services, especially peer support groups. Patients who want to try new forms of therapy should do so early in the course of the disease when these therapies are most likely to be effective and the patient has the least to lose if the therapy proves ineffective. This is especially true because the use of the most effective regimens at a time when the patient is asymptomatic may mean that the patient is resistant to most or all therapies of proven value when most in need of palliation.

Breast Neoplasms↗
PubMed1990

Adjuvant systemic therapy.

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Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Adjuvant systemic therapy for patients with node-negative tumors.

Early adjuvant therapy studies, especially adjuvant chemotherapy studies, were performed almost exclusively on patients with histologically involved axillary lymph nodes ("node-positive" patients). These therapies were restricted to this group of patients because the toxicities of adjuvant therapy were believed too great to justify its use in patients with a very good prognosis until its benefits were fully established. However, after it was demonstrated that adjuvant therapy can significantly prolong the disease-free survival of almost all groups of node-positive patients and the overall survival of some patient subsets, adjuvant therapy trials specifically designed for patients without histologically involved lymph nodes ("node-negative" patients) were initiated. Results from some of the largest of these second generation trials were recently published, and the early results from these studies have generated new questions. For example, will the mature results from these studies be nearly identical to the results seen in node-positive patients, or will node-negative patients derive greater benefits from adjuvant therapy? Is it possible that adjuvant therapy will "cure" node-negative patients but not node-positive patients? (Cure is defined here as an effect of therapy that returns a patient to the life expectancy she might have had if she had never been diagnosed with breast cancer). Is it possible that the added years of life from adjuvant therapy or that the number of node-negative patients who benefit are so small that these benefits will be outweighed by delayed toxicities that appear in patients who might have been cured even without adjuvant therapy? At present the available data to answer these questions definitely are either contradictory or nonexistent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Adjuvant chemotherapy of breast cancer.

Many women will not be cured of breast cancer by even the best early detection and surgical techniques because of micrometastases present at diagnosis. Adjuvant therapy has extended the disease-free interval for most patients and lengthens overall survival for many. Combination chemotherapy has become the standard form of adjuvant treatment for premenopausal women with breast cancer and positive lymph nodes after primary therapy. With minimal toxicity, disease-free and overall survival are improved. Results are less impressive or less clear-cut for postmenopausal women or any woman with negative lymph nodes. Long-term toxicities of adjuvant chemotherapy may include second malignancies and cardiac dysfunction. Although these complications probably are rare, they must be considered seriously when weighing chemotherapy for patients in whom its benefits may be slight. Innovations likely to become standard in adjuvant therapy decision making include risk assessment with new prognostic indicators (growth fraction, oncogene expression) and investigation of dose intensification using bone marrow growth factors and autologous stem-cell support.

Antineoplastic Combined Chemotherapy Protocols↗