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Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and theleading cause of cancer death among women.

Many early breast carcinomas may be asymptomatic; pain or discomfort is not usually a symptom ofbreast cancer. Breast cancer is often first detected as an abnormality on a mammogram before it is feltby the patient or healthcare provider. The general approach to evaluation of breast cancer has becomeformalied as triple assessment! clinical e"amination, imaging #usually mammography and$orultrasonography%, and needle biopsy. #&ee Wor'up.%

(ncreased public awareness and improved screening have led to earlier diagnosis, at stages amenableto complete surgical resection and curative therapies. )onsequently, survival rates for breast cancerhave improved significantly, particularly in younger women.

&urgery is considered primary treatment for breast cancer. Many patients with early-stage breast cancerare cured with surgery alone. #&ee Treatment and Management.%

*d+uvant treatment of breast cancer is designed to treat micrometastatic disease, or breast cancer cellsthat have escaped the breast and regional lymph nodes but which have not yet had an establishedidentifiable metastasis. epending on the model of ris' reduction, ad+uvant therapy has been estimatedto be responsible for -/01 of the reduction in mortality rate. 2ver the last 0 decades, breast cancerresearch has led to e"traordinary progress in our understanding of the disease, resulting in more efficientand less to"ic treatments. #&ee Treatment and Management.%

The breasts of an adult woman are mil'-producingglands situated on the front of the chest wall. Theyrest on the pectoralis ma+or muscle and aresupported by and attached to the front of the chestwall on either side of the sternum by ligaments.3ach breast contains 4-05 lobes arranged in acircular fashion. The fat that covers the lobesgives the breast its sie and shape. 3ach lobecomprises many lobules, at the end of which areglands where mil' is produced in response tohormones #see the image below%.

The current understanding of breasttumorigenesis is that invasive cancers arisethrough a series of molecular alterations at thecellular level, resulting in the outgrowth andspread of breast epithelial cells with immortalfeatures and uncontrolled growth.

6enomic profiling has demonstrated the presenceof discrete breast tumor subtypes with distinctclinical behavior #eg, 7 subclasses! luminal *,luminal B, basal, and human epidermal growth

factor receptor 0 893:0-positive%. The e"actnumber of disease subtypes and molecularalterations from which these subtypes deriveremains to be fully elucidated, but they generallyalign closely with the presence or absence ofhormone receptor and mammary epithelial celltype #luminal or basal%.

The figure below summaries the current general understanding of breast tumor subtypes, prevalence,and the ma+or associated molecular alterations. This view of breast cancer--not as a set of stochasticmolecular events, but as a limited set of separable diseases of distinct molecular and cellular origins--has altered thin'ing about breast cancer etiology, type-specific ris' factors, prevention, and treatmentstrategies.

3pidemiologic studies have identified many ris' factors that increase the chance of a woman developingbreast cancer. 6o to Breast )ancer :is'

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screening, dietary changes, and decreased activity.

*lthough breast cancer incidence is on the rise globally, breast cancer mortality has been decreasing,especially in industrialied countries. The 0550 international female breast cancer incidence rates variedby more than 0-fold, ranging from .= cases per 455,555 in Moambique to 454.4 cases per 455,555 inthe >nited &tates. (n 055?, the *merican )ancer &ociety #*)&% estimated there were nearly 4.7 millionnew cases of invasive breast cancer worldwide.

(n the >&, appro"imately 05/,5=5 new cases of female invasive breast cancer were predicted to occur in0545, along with 4,=/5 cases in men.84 (n addition to invasive breast cancer, 7,545 new cases of insitu breast cancer were e"pected to occur among women, of which appro"imately ?1 were e"pected tobe ductal carcinoma in situ #)(&%.

*fter 0 decades of increasing incidence rates, the number of new female breast cancers decreased by0.01 per year from 4=== to 055. This decrease is thought to reflect reduced use of 9:T following thepublication of the W9( findings in 0550, which lin'ed 9:T use to an increased ris' of heart disease andbreast cancer. :ates of )(& have stabilied since 0555.80

The current lifetime ris' of breast cancer in the >& is estimated at 40./1 for all women, 4.1 for non-9ispanic whites, and =.=?1 for blac' women. 2verall, the annual incidence rates in blac' women#44=.7$455,555% and 9ispanic$@atina women #?=.=$455,555% have been stable since the early 4==5s, andthey are lower than the annual incidence of breast cancer in white women #474.4$455,555%. 9owever,blac' women are more li'ely than white women to be diagnosed with larger, advanced-stage tumors #Acm%.

*lthough incidence rates among *sian and acific (slander women have continued to increase at 4.1per year #?=$455,555%, they are still significantly lower than the rates in white women. Capanese andTaiwanese woman have one fifth the ris' of >& women.8

The various types of breast cancers are listed below by percentage of cases!

(nfiltrating ductal carcinoma is the most commonly diagnosed breast tumor and has a tendency tometastasie via lymphatics; this lesion accounts for /1 of breast cancers*ppro"imately D7,555 cases of )(& are diagnosed annually in the >&2ver the last 0 years, lobular carcinoma in situ #@)(&% incidence has doubled and is currently 0.? per455,555 women; the pea' incidence is in women aged 75-5 years(nfiltrating lobular carcinoma comprises less than 41 of invasive breast cancersMedullary carcinoma accounts for about 1 of cases and generally occurs in younger womenMucinous #colloid% carcinoma is seen in fewer than 1 of invasive breast cancer cases.Tubular carcinoma of the breast is comprises 4-01 of all breast cancersapillary carcinoma is usually seen in women older than D5 years and accounts for appro"imately 4-01of all breast cancersMetaplastic breast cancer accounts for less than 41 of breast cancer cases, tends to occur in older

women #average age of onset in the si"th decade%, and has a higher incidence in blac'sMammary aget disease comprises 4-71 of all breast cancers and has a pea' incidence in the si"thdecade of life #mean age, / y%eath rates from breast cancer in the >nited &tates have decreased steadily in women since 4==5. Thebreast cancer mortality rate fell 071 between the years 4==5 and 0555 for women aged 5-/= years.The largest decrease in mortality has been seen in women younger than 5 years #.1 per year%compared with those aged 5 years and older #0.51 per year%.

The decrease in breast cancer death rates is thought to represent progress in both earlier detection andimproved treatment modalities.84 The 0545 estimates were 75,05 e"pected breast cancer deaths#=,?75 women, =5 men%.84

rognostic and redictive

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Breast cancer prognostic factors include the following!

*"illary lymph node statusTumor sie@ymphatic$vascular invasionatient age9istologic grade9istologic subtypes #eg, tubular, mucinous 8colloid, papillary%

:esponse to neoad+uvant therapy3:$ : status93:0 gene amplification and$or overe"pression #see below%#*lso see Breast )ancer and 93:0.%Breast cancer predictive factors include the following!

3:$: status93:0 gene amplification and$or overe"pression)ancerous involvement of the lymph nodes in the a"illa is an indication of the li'elihood that the breastcancer has spread to other organs. &urvival and recurrence are independent of level of involvement butdirectly related to the number of involved nodes.

atients with node-negative disease have an overall 45-year survival rate of /51 and a -yearrecurrence rate of 4=1. (n patients with lymph nodes that are positive for cancer, the recurrence rates at years are as follows!

4- positive nodes! 5-7517-= positive nodes! 77-/51More than 45 positive nodes! /0-?019ormone-positive tumors have a more indolent course and are responsive to hormone therapy. 3: and: assays are routinely performed on tumor material by pathologists, and immunohistochemistry #(9)%is a semiquantitative technique that is observer and antibody dependent.

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6o to Breast )ancer and 93:0 for complete information on this topic.

uctal carcinoma in situ)(& is divided into comedo #ie, cribriform, micropapillary, solid% and noncomedo subtypes, whichprovides additional prognostic information on the li'elihood of progression or local recurrence, as shownin Table 4, below.

Table 4. uctal )arcinoma in &itu &ubtypes #2pen Table in a new window%

)(& )haracteristic )omedo EoncomedoEuclear grade 9igh @ow3strogen receptor Eegative ositive93:0 overe"pression resent *bsentistribution )ontinuous MultifocalEecrosis resent *bsent@ocal recurrence 9igh @owrognosis Worse Better

@obular carcinoma in situ*ppro"imately, 45-051 of women with @)(& develop invasive breast cancer within 4 years after their@)(& diagnosis. Thus, @)(& is considered a biomar'er of increased breast cancer ris'.

(nfiltrating ductal carcinoma(nfiltrating ductal carcinoma is the most commonly diagnosed breast tumor and has a tendency tometastasie via lymphatics.

(nfiltrating lobular carcinoma@i'e ductal carcinoma, infiltrating lobular carcinoma typically metastasies to a"illary lymph nodes first.9owever, it also has a tendency to be more multifocal. espite this, the prognosis is comparable to thatof ductal carcinoma.

Medullary carcinoma:oughly 51 of patients have lymph node metastasis. Typical or classic medullary carcinomas are oftenassociated with a good prognosis despite the unfavorable prognostic features associated with this typeof breast cancer. 9owever, an analysis of D5= medullary breast cancer specimens from various stage (and (( Eational &urgical *d+uvant Breast and Bowel ro+ect #E&*B% protocols indicates that overallsurvival and prognosis are not as good as previously reported.

Mucinous carcinoma2verall, patients with mucinous carcinoma have an e"cellent prognosis, with a greater than ?51 45-yearsurvival.

Tubular carcinoma

This type of breast cancer has a low incidence of lymph node involvement and a very high overallsurvival rate. Because of its favorable prognosis, patients are often treated with only breast-conservingsurgery and local radiation therapy.

apillary carcinoma)ystic papillary carcinoma has a low mitotic activity, which results in a more indolent course and goodprognosis. 9owever, invasive micropapillary ductal carcinoma has a more aggressive phenotype, eventhough appro"imately /51 of cases are 3:-positive.

* retrospective review of 4,755 cases of invasive carcinoma identified ? cases #D1% with at least onecomponent of invasive micropapillary ductal carcinoma. *dditionally, lymph node metastasis is seenfrequently in this subtype #/5-=51 incidence%, and the number of lymph nodes involved appears to

correlate with survival.

Metaplastic breast cancerThe ma+ority of published case series have demonstrated a worse prognosis for MB) as compared with

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infiltrating ductal carcinoma, even when ad+usted for stage, with a -year overall survival rate of 7?-/41and -year disease-free survival rate of 4-D51. (n most case series, large tumor sie and advancedstage have emerged as predictors of poor overall survival and prognosis. Eodal status does not appearto impact survival in metaplastic breast cancer.

Mammary aget diseaseM is associated with an underlying breast cancer in /1 of cases. Breast-conserving surgery canachieve satisfactory results, but at the ris' of local recurrence. *d+uvant chemotherapy with tamo"ifen

may increase survival in premenopausal patients with lymph node metastasis. oor prognostic factorsinclude a palpable breast tumor, lymph node involvement, histologic type, and patient younger than D5years. The overall -year and 45-year survival rates are =1 and 771, respectively.

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