Hormonotherapy in Precancerous Lesions. shani breuer, MD, MHA Sharett - Institute of Oncology Hadassah Hebrew University Medical Centers
Nov 01, 2014
Hormonotherapy in Precancerous Lesions.
shani breuer, MD, MHA
Sharett - Institute of Oncology Hadassah Hebrew University Medical Centers
Precancerous Lesions
• Ductal carcinoma in situ (DCIS) • Lobular carcinoma in situ (LCIS) • atypical lobular hyperplasia (ALH) • atypical lobular hyperplasia (ALH)
DCIS -‐ Ductal carcinoma in situ
• ductal carcinoma in situ (DCIS) has become one of the most commonly diagnosed breast condi;ons.
• lack of understanding of its natural history and the inability to determine which DCIS will progress to invasive carcinoma.
• Cancer-‐specific survival for the woman diagnosed with DCIS exceeds 95%, regardless of the type of local therapy employed.
• Mastectomy / excision alone and excision plus RT is curaAve in approximately 98% of pa;ents regardless of age, DCIS presenta;on, size, or grade.
Endocrine Therapy -‐ DCIS
• ER is present in about 80% of DCIS lesions. • two poten<al benefits : -‐ Reduc;on in local recurrence aNer BCT. -‐ preven;on of the development of new primary breast cancers in the contralateral breast.
• Two trials: NSABP B-‐24 trial & UK/ANZ trial.
LCIS -‐ Lubolar carcinoma in situ
• 1941 – first described. • In the past, LCIS was most frequently diagnosed in women aged 40 to 50, a decade earlier than DCIS, but recent literature indicates that the incidence in postmenopausal women is increasing.
• typically not associated with microcalcifica;ons on mammography.
• LCIS is both mulAfocal and bilateral in a large percentage of cases.
• Typically posiAve for ER and PR, lacks expression of E-‐cadherin.
LCIS -‐ Lubolar carcinoma in situ • women with LCIS have anywhere from a 3.0-‐ to 8.0-‐fold
higher risk of breast cancer • 10 years folow up: 15% had ipsilateral invasive ca 9.3% had contralateral invasive ca. • 1% to 2% per year Increased rate of development of
invasive ca (with a life;me risk of 30% to 40% ), and 5.7% of the pa;ents developed metasta;c breast cancer.
• Management (When LCIS is seen on an excised ;ssue, it is not necessary to
obtain nega;ve -‐margins of resec;on, and there is no established role for radia;on therapy in pa;ents with LN).
• 1992 NSABP started, examined the ability of tamoxifen to prevent breast cancer in women at increased risk.
• From 13,388 women randomized for this trail 826 had LCIS: risk reduc;on was 56 % .
• The benefits of tamoxifen were most prominent in par;cipants with a history of lobular carcinoma in situ and atypical hyperplasia.
• The major toxicity was an increase in the rate of endometrial cancer (risk ra;o 2.53, 95% CI: 1.35±4.97), as previously demonstrated in treatment trials with tamoxifen.
• The rates of stroke, pulmonary embolism and deep vein thrombosis were elevated in the tamoxifen group. Toxici;es were most evident in women over 50 years of age
• prospective, double-blind, randomized clinical trial conducted beginning July 1, 1999, in nearly 200 clinical centers throughout North America. • 19, 747 postmenopausal women of mean age 58.5 years with increased 5-year breast cancer risk. • Intervention Oral tamoxifen (20 mg/d) or raloxifene (60 mg/d) over 5 years.
• The trial established that in post-‐menopausal women, 5 years of raloxifene was almost as efficacious as tamoxifen, decreasing invasive and non-‐invasive breast cancer risk by about 38 %
• 893 par<cipants gave a history of LCIS, and their rates of subsequent breast cancer were similar with tamoxifen and raloxifene
ADH -‐ atypical hyperplasia
• While some studies have shown no difference in breast cancer risk between ADH and ALH, most suggest that the risk is greater with ALH
• The odds raAo (OR) for developing breast cancer in women with ADH compared with women without ranges from 1.47 to 4.88, whereas the OR with ALH ranges from 4.21 to 5.71
ADH -‐ atypical hyperplasia
NSABP P1 trial: • 49% risk reduc;on was seen with tamoxifen. • The benefits of tamoxifen were observed for both invasive and noninvasive carcinoma and were seen in women of all ages. • A par;cular benefit was seen in those at risk because of atypical hyperplasia, with an 84% reducAon in cancer incidence in this group.
Management of the High-‐Risk PaAent
no formal defini;on of what cons;tutes high risk. • BRCA. • These include premenopausal women, younger postmenopausal women without a uterus, and those at risk on the basis of atypical hyperplasia or LCIS.
• exemestane in invasive and pre-‐invasive breast cancer in postmenopausal women.
• 4560 women with at least one of the following: Age > 60 years; Gail score > 1.66; a prior diagnosis of atypical ductal hyperplasia (ADH), lobular hyperplasia (ALH), lobular carcinoma in-‐situ or ductal carcinoma in-‐situ (DCIS) treated with mastectomy.
• At a median follow-‐up of 3 years: Risk reducAon of 65% (P = 0.002).
MAP.3 Trial