Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (78 page)

•
Systemic therapy:
for stage I-III except tumors <1 cm (complex risk assessment needed).
http://www.adjuvantonline.com/index.jsp
can guide use of chemo and/or hormonal Rx.

Chemotherapy
(
Lancet
2008;371:29): in neoadjuvant setting usually
anthracycline
-based (eg,
a
driamycin +
c
yclophosphamide). Sequential Rx w/
taxane
(eg, paclitaxel) → small ↑ survival (
NEJM
2007;357:1496; 2010;362:2053 & 2010;363:2200).

Anti-HER2 therapy
(growing list of agents) in
HER2
tumors (
NEJM
2012;366:176)

trastuzumab
(Herceptin; anti-
HER2
mAb) ↑ survival (
NEJM
2001;344:783); give after anthracycline or w/ taxane to avoid cardiotox (
JCO
2002;20:125 &
NEJM
2011;365:1273) lapatinib (tyrosine kinase inhib. of
HER2
&
EGFR
) + trastuzumab ↑ survival after failing trastuzumab (
JCO
2012;30:2585); dual inhib. initial Rx ↑ response (
Lancet
2012;379:633) pertuzumab (anti-
HER2
mAb, prevents dimerization) ↑ progression-free survival when added to trastuzumab as first-line Rx for metastatic dis. (
NEJM
2012;366:109) trastuzumab emtansine (T-DM1,
HER2
mAb conjugated to microtubule inhibitor) ↑ survival compared to second-line lapatinib + capecitabine (
NEJM
2012;367:1783)

Bevacizumab
(anti-VEGF): ? in neoadjuvant Rx if
HER2
(
NEJM
2012;366:299 & 310)

Hormonal (in ER/PR
or unknown status)

tamoxifen
: 39% ↓ recurrence and 30% ↓ breast cancer mortality in pre-and postmenopausal patients; 10 y of Rx superior to 5 y (
Lancet
2011;378:771 & 2013;381:805)

aromatase inhibitors (AI)
(anastrozole, letrozole, exemestane): ~18% ↓ recurrence vs. tamoxifen in
postmenopausal
Pts (
Lancet
2005;365:60;
NEJM
2005;353:2747)

everolimus ↑ progression-free survival if postmenopausal & failed AI (
NEJM
2012;366:520)

2nd-line: ovarian ablation with LHRH agonists (goserelin) or oophorectomy if
premenopausal
; pure antiestrogens (fulvestrant) if
postmenopausal

Prevention
(with selective estrogen receptor modulator [SERM] or AI)
• Tamoxifen: ↓ risk contralat. breast CA as adjuvant Rx.  Approved for 1° prevent. if ↑ risk: ↓ invasive breast ca, but ↑ DVT & uterine CA; ? ↑ in mortality (
Lancet
2002;360:817 ).

• Raloxifene: ↓ risk of invasive breast cancer & vertebral fx, ↑ risk of stroke & DVT/PE (
NEJM
2006;355:125);
tamoxifen in prevention of breast cancer w/ ↓ risk of DVT/PE & cataracts, trend toward ↓ uterine cancer (  
JAMA
2006;295:2727 ) • Exemestane in high-risk postmenopausal ↓ invasive breast ca by 65% (
NEJM
2011;364:2381) •
BRCA1/2
: intensified surveillance as described above. Prophylactic bilat. mastectomy → ~90% ↓ risk; bilat. salpingo-oophorectomy ↓ risk of ovarian
and
breast cancer.

PROSTATE CANCER

Epidemiology and risk factors
(
NEJM
2003;349:366)
• Most common cancer in U.S. men; 2nd most common cause of cancer death in men • Lifetime risk of prostate cancer dx
16%; lifetime risk of dying of prostate cancer
3%

• More common with ↑ age (rare if <45 y), in African Americans and if
FHx • ↑ risk w/
BRCA2
(4.7) and
BRCA1
(1.8) (
JNCI
1999;91:1310 & 2002;94:1358)
Clinical manifestations
(usually asymptomatic at presentation)
•
Obstructive sx
(more common with BPH): hesitancy, ↓ stream, retention, nocturia •
Irritative sx
(also seen with prostatitis): frequency, dysuria, urgency • Periprostatic spread: hematuria, hematospermia, new-onset erectile dysfunction • Metastatic disease: bone pain, spinal cord compression, cytopenias
Screening
(
NEJM
2012;367:e11)
•
Digital rectal exam
(DRE): size, consistency, lesions •
PSA:
4 ng/mL cut point neither Se nor Sp; can ↑ with BPH, prostatitis, acute retention, after bx or TURP, and ejaculation (
no significant
↑
after DRE, cystoscopy
); 15% of men >62 y w/ PSA <4 & nl DRE have bx-proven T1 cancer (
NEJM
2004;350:2239) • Per American Cancer Soc. men ≥50 y (or ≥ 45 y if African-Am or
FHx) should discuss PSA screening w/ their MD; USPSTF rec. against screening in asx males (no reduction in prostate cancer-related mortality) (
NEJM
2009;360:1310;
Annals
2012;157:120)
Diagnostic and staging evaluation

•
Transrectal ultrasound
(TRUS)
guided biopsy
, with 6–12 core specimens •
Histology
:
Gleason grade
(2–10; low grade ≤6) = sum of the differentiation score (1 = best, 5 = worst) of the 2 most prevalent patterns in the bx; correlates with prognosis •
Imaging
: to evaluate extraprostatic spread bone scan: for PSA >10 ng/mL, high Gleason grade or clinically advanced tumor abdomen-pelvis CT: inaccurate for detecting extracapsular spread and lymph node mets endorectal coil MRI: improves assessment of extracapsular spread