BREAST CANCER
The
management of primary breast cancer has undergone a remarkable evolution as a
result of major efforts at early diagnosis (through encouragement of
self-examination as well as throughthe use of cancer detection centers) and the
implementation of combined modality approaches incorporating systemic
chemo-therapy as an adjuvant to surgery and radiation therapy. Women with stage
I disease (small primary tumors and negative axillary lymph node dissections)
are currently treated with surgery alone, and they have an 80% chance of cure.
Women with
node-positive disease have a high risk of both local and systemic recurrence.
Thus, lymph node status directly indicates the risk of occult distant
micrometastasis. In this situation, postop-erative use of systemic adjuvant
chemotherapy with six cycles of cyclophosphamide, methotrexate, and
fluorouracil (CMF proto-col) or of fluorouracil, doxorubicin, and
cyclophosphamide (FAC) has been shown to significantly reduce the relapse rate
and prolong survival. Alternative regimens with equivalent clinical benefit
include four cycles of doxorubicin and cyclophosphamide and six cycles of
fluorouracil, epirubicin, and cyclophosphamide (FEC). Each of these
chemotherapy regimens has benefited women with stage II breast cancer with one
to three involved lymph nodes. Women with four or more involved nodes have had
limited benefit thus far from adjuvant chemotherapy. Long-term analysis has
clearly shown improved survival rates in node-positive premeno-pausal women who
have been treated aggressively with multiagent combination chemotherapy. The
results from three randomized clinical trials clearly show that the addition of
trastuzumab, a monoclonal antibody directed against the HER-2/neu receptor, to anthracycline- and
taxane-containing adjuvant chemotherapy ben-efits women with
HER-2-overexpressing breast cancer with respect to disease-free and overall
survival.
Breast
cancer was the first neoplasm shown to be responsive to hormonal manipulation.
Tamoxifen is beneficial in postmeno-pausal women when used alone or in
combination with cytotoxic chemotherapy. The present recommendation is to
administer tamoxifen for 5 years of continuous therapy after surgical
resec-tion. Longer durations of tamoxifen therapy do not appear to add
additional clinical benefit. Postmenopausal women who complete 5 years of
tamoxifen therapy should be placed on an aromatase inhibitor such as
anastrozole for at least 2.5 years, although the optimal duration is unknown.
In women who have completed 2–3 years of tamoxifen therapy, treatment with an
aromatase inhibitor for a total of 5 years of hormonal therapy is now
recom-mended .
Results
from several randomized trials for breast cancer have established that adjuvant
chemotherapy for premenopausal women and adjuvant tamoxifen for postmenopausal
women are of benefit to women with stage I (node-negative) breast cancer. While
this group of patients has the lowest overall risk of recurrence after surgery
alone (about 35–50% over 15 years), this risk can be fur-ther reduced with adjuvant
therapy.
The approach to women
with advanced breast cancer remains a major challenge, as current treatment
options are only palliative. Combination chemotherapy, endocrine therapy, or a
combination of both results in overall response rates of 40–50%, but only a 10–20%
complete response rate. Breast cancers expressing estro-gen receptors (ER) or
progesterone receptors (PR), retain the intrinsic hormonal sensitivities of the
normal breast—including the growth-stimulatory response to ovarian, adrenal,
and pituitary hormones. Patients who show improvement with hormonal abla-tive
procedures also respond to the addition of tamoxifen. The aromatase inhibitors
anastrozole and letrozole are now approved as first-line therapy in women with
advanced breast cancer whose tumors are hormone-receptor positive. In addition,
these agents and exemestane are approved as second-line therapy following
treatment with tamoxifen.
Patients with
significant involvement of the lung, liver, or brain and those with rapidly
progressive disease rarely benefit from hor-monal maneuvers, and initial
systemic chemotherapy is indicated in such cases. For the 25–30% of breast
cancer patients whose tumors express the HER-2/neu cell surface receptor, the human-ized monoclonal anti-HER-2/neu antibody, trastuzumab, is avail-able
for therapeutic use alone or in combination with cytotoxic chemotherapy.
About 50–60% of
patients with metastatic disease respond to initial chemotherapy. A broad range
of anticancer agents have activity in this disease, including the
anthracyclines (doxorubicin, mitoxantrone, and epirubicin), the taxanes
(docetaxel, paclitaxel, and albumin-bound paclitaxel) along with the
microtubule inhib-itor ixabepilone, navelbine, capecitabine, gemcitabine,
cyclophos-phamide, methotrexate, and cisplatin. The anthracyclines and the
taxanes are two of the most active classes of cytotoxic drugs. Combination
chemotherapy has been found to induce higher and more durable remissions in up
to 50–80% of patients, and anthra-cycline-containing regimens are now
considered the standard of care in first-line therapy. With most combination
regimens, partial remissions have a median duration of about 10 months and
com-plete remissions have a duration of about 15 months. Unfortunately, only
10–20% of patients achieve complete remissions with any of these regimens, and
as noted, complete remissions are usually not long-lasting.
Prostate cancer was
the second cancer shown to be responsive to hormonal manipulation. The
treatment of choice for patients with advanced prostate cancer is elimination
of testosterone production by the testes through either surgical or chemical
castration. Bilateral orchiectomy or estrogen therapy in the form of
diethylstilbestrol was previously used as first-line therapy. Presently, the
use of luteinizing hormone-releasing hormone (LHRH) agonists— including
leuprolide and goserelin agonists, alone or in combina-tion with an
antiandrogen (eg, flutamide, bicalutamide, or nilutamide)—is the preferred
approach. There appears to be no survival advantage of total androgen blockade
using a combination of LHRH agonist and antiandrogen agent compared with
single-agent therapy. Hormonal treatment reduces symptoms—especially bone
pain—in 70–80% of patients and may cause a significant reduction in the
prostate-specific antigen (PSA) level, which is now widely accepted as a
surrogate marker for response to treatment in prostate
cancer. Although initial hormonal manipulation is able to control symptoms for
up to 2 years, patients usually develop pro-gressive disease. Second-line
hormonal therapies include aminoglu-tethimide plus hydrocortisone, the
antifungal agent ketoconazole plus hydrocortisone, or hydrocortisone alone.
Unfortunately, nearly
all patients with advanced prostate cancer eventually become refractory to
hormone therapy. A regimen of mitoxantrone and prednisone is approved in
patients with hor-mone-refractory prostate cancer because it provides effective
pallia-tion in those who experience significant bone pain. Estramustine is an
antimicrotubule agent that produces an almost 20% response rate as a single
agent. However, when used in combination with either etoposide or a taxane such
as docetaxel or paclitaxel, response rates are more than doubled to 40–50%. The
combination of doc-etaxel and prednisone was recently shown to confer survival
advan-tage when compared with the mitoxantrone-prednisone regimen, and this
combination has now become the standard of care for hormone-refractory prostate
cancer.
Related Topics
Privacy Policy, Terms and Conditions, DMCA Policy and Compliant
Copyright © 2018-2024 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.