Carcinoma Breast



Incidence
The incidence of cancer Breast is slightly increasing, coming very close to that of Ca Cervix, which is the common cancer in women. It is the most common cause of mortality in woman aged 40 to 55. Incidence increases with age, peaking in the sixth decade.
Predisposing Factors.
There are a large number of predisposing factors or risk factors  which increase the possibility of getting Ca Breast. However only ten percent of patients have any of these factors. Hereditary, genetic predisposition, hormonal factors and diet etc are few of these risk factors.
Strong family history of Ca breast in mother, sister and maternal aunt, presence of mutation of BRCA 1 or BRCA 2 gene, early menarche, nulliparity, late menopause, excessive use of estrogens, increase the risk.. Atypical Hyperplasia increase the risk too.
Late menarche, first child at or before 18 years of age, early menopause, and opherectomy before 35 years, decrease the risk.
There is an increase risk in American women and ladies of the upper social economic class. Excessive use of fat, alcohol and cholesterol rich diet and exposure to radiation may increase risk too.
Past history of Ca Breast the opposite side is the biggest risk factor.
Pathology
Carcinoma Breast generally arises from the Terminal Duct Lobular Unit ( TDLU )More than 95% cancers are adenocarcinomas,being Ductal or Lobular,Each of these can be Invasive or in-situ. invasive ductal carcinoma( IDC )is most common being found in over 80% cases, The most common variety of IDC is Not Other vice Specified( NOS)found in over 80% of cases of IDC, Other types of IDC are tubular, papillary, comadoe, medulary and colloid .DCIS, LCIS and ILC are found in less than 5 % Ca Breast spreads by lymphatics and by haematogenous route. Metastasis to axillary lymph nodes are found in almost 40-50%caes at time of presentation ,though internal mammary chain and supraclavicular nodes may be involved in less than 5%.
Common sites of distant spread are Liver, Lung, Bone and Brain. Pelvic deposits may be seen in advanced cases due to transcoelomic spread
Prognostic Factors
Though there is a long list of prognostic factors today, age nodal status and tumor size remain the three main prognostic factors.
Young age, large tumour and involvement of axillary nodes, gravely effect prognosis.
Histological type and grade, lymphatic and vascular invasion, proliferative index, S phase fraction, ploidy are other factors that effect prognosis.
Over expression of c- erb B-2 ECG factor, Cathepsin D and mutated P53 are poor prognostic factors, while over expressed bcl 2, Nm 23 gene and PS2 factors improve prognosis.


Clinical Presentation
Lump breast is the most common form of presentation of carcinoma breast. Axillary lymphadenopathy, nipple retraction, nipple discharge and skin involvement may be the other presentations. Rarely patient may present only with axilary or supraclavicular nodes only or bony pain.
Investigations
FNAC of the lump and the axillary nodes is the best diagnostic tool. This combined with Tru cut biopsy yields a diagnosis in more that 95%. Mammography and ultrasound are helpful in localising small tumours and cases presenting with nipple retraction and discharge or axillary lymphadenopathy without a breast lump .However Mammography should be done in all cases of carcinoma breast, specially when breast conserving surgery is being planned, to rule out multifocal and bilateral disease and to have a baseline for followup of opposite breast. Image guided Needle biopsy or lumpectomy with frozen section may have to be resorted to in rare cases for diagnosis,where FNAC or Tru Cut have been inconclusive. Breast MRI and Radionucilide imaging are rarely needed in clinical practice in situation of T0Ni disease.
While X-ray chest and ultrasound of abdomen are adequate for the metasatatic work up of early Ca Breast, bone scan should be done for all patients of locally advanced or metasatatic carcinoma breast.
All operative specimens should be checked for ER PR and HER 2 recoptors, Cases of LABC ,being managed with NACT, should undergo trucut biopsy for these tests
TNM Staging
Primary Tumour (T)
TX        -    Primary tumor cannot be assessed
T1S        -    Carcinoma in site
T1        -    Tumor less than 2 cm
T2        -    Tumor 2-5 cm
T3        -    Tumor more than 5 cm
T4        -    (a) Extension to chest wall
(b) Peau d’orange, ulceration    or satellite nodule
(c) 4a + 4 b
(d) Inflammatory Ca Carcinoma.
Regional lymph node (N)
Nx -    Regional lymphnodes cannot be assessed
N1-    Metastasis to movable ipsilateral lymphnodes
N2 -    Metastatic ipsilateral lymphnodes stuck to each other or other axillary             structures.
N3 -    Metastasis to ipsilateral internal mammary or supraclavicular lymph             node
Distant Metastasis (M)
Mx -    Distant metastasis cannot be assessed
Mo -    No distant metastasis
M1 -    Distant metastasis


Stage Grouping
Stage O    Tis              N0    M0
Stage 1    T1                N0    M0
Stage IIA  T0,  T1        N1    M0
Stage IIB  T2                N1    M0
T3                N0    M0
Stage IIIA  T0 T1 T2    N2    M0
T3                N1, N2    M0
Stage IIIB    T4    Any N    M0
Any T    N3    M0
Stage IV    Any T    Any M    M1
Clinical Group Staging – This is more commonly used
(a)    Early Ca Breast – T1, T2, N1, Mo
(b)    Locally advanced Ca Breast – T3, T4 Any N Mo  Any T N2, 3 Mo
(c)    Metastatic Ca Breast – Any T, Any N M1
Regional Lymphnodes -  There are two groups of lymph nodes that drain the breast.
1.    Axillary lymphnodes- This group includes the interpectoral (Rotors nodes) and nodes along the axillary vein and its tributaries. These are divided into three groups.
(a)    Level (low axilla) – lymph nodes lateral to the lateral border of pectorals minor
(b)    Level II (Midaxilla) – Lymph nodes between the medial and lateral border of pectorals minor, (under it) and the interpectoral group.
(c)    Level II (Apical axilla) – Lymph nodes medial to the medial margin of pectoralis  minor
2. Internal Mammary lymph nodes, in the intercostal spaces, along the edge of sternum.

Management of early Carcinoma Breast
Surgery remains the mainstay of treatment in early carcinoma breast.
Breast conserving surgery-Lumpectomy,Axillary Clearance followed by radiotherapy
Modified Radical Mastectomy
Contraindications for BCT
•    Pregnancy
•    Two lesions in different quadrants
•    Extensive DCIS
•    Unfit for radiotherapy
•    Non availability of radiotherapy
•    Small breast-lump ratio
•    Unwillingness of patient
Adjuvant Therapy in Early Ca Breast
Chemotherapy - Indications for adjuvant chemotherapy in early Ca Breast are-
•    All premenopausal women and perimenopausal women
•    All node positive cases
•    Tumour size more that 1 cm
•    Young post menopausal ER PR negative women even with T1b No disease.
Infact most patients need adjuvant chemotherapy, expect post menopausal ladies with ER PR positive, T1bNo diseases, or very elderly ladies with node negative disease and favorable history like mucinous tubular or papillary carcinoma.
Chemotherapeutic Regimes – The commonly used chemotherapeutic regimes are anthracyclin( Adriamycin or epirubicin) based.  Four to six cycles of CAF (Cyclophosphamide , Adriamycin and 5-FU) AC ,FEC or EC are normally given.  
Radiation - external beam radiation to the chest wall and para glandular area is recommended for following situations
•    Involvement of skin or muscle
•    Residual disease
•    Positive margins
•    Tx or PT3 lesion
•    More than three nodes positive
•    Perinodal spread
•    Vascular or lymphatic spread
•    More that 25% of nodes positve if the number of nodes removed is less than 5
•    Axilla is included in radiotherapy field if
•    N2 disease
•    Residual nodal disease
Posterior axillary boost given if more that 10 nodes positive
Radiotherapy in BCT is part of primary treatment.
Sequence of chemotherapy and radiotherapy
•    If Radiotherapy is to be given for residual disease or positive margins, then it should be given after one cycle of chemotherapy ,and followed by remaining chemotherapy
•    If Radiotherapy is indicated for  nodal involvement, or T3 T4 lesion, or muscle or skin involvement, then 3-4 cycles or all cycles of chemotherapy should be given before radiotherapy
•    It is however preferable to give radiotherapy within 14-16 weeks of surgery
Hormonal Therapy
Tamoxifien is the most common hormonal treatment used. Indicated in all patients who are ER PR positive, irrespective of menopausal status, in doses of 10 mg BD for five years. Tamoxifen preferably to be started after completion of chemotherapy and radiotherapy where indicated.Aromitase inhibitors like Letrozole to be given to these patients for 2-5 years after completion of Tamoxifen, or if they have recurrence while on, or after Tamoxifen
Locally Advanced Breast Carcinoma (LABC)
LABC (T3 or T4 with any N or Any T with N2 or N3 and M0 ) are managed with all three modalities ,Surgery, Chemotherapy and Radiotherapy. The sequence of these to be tailor made to suit the patient.
If the tumour is operable, then the patient undergoes surgery (Mastectomy or lumpectomy and Axillary clearance) followed by chemotherapy and radiotherapy.
Cases which are non operable at time or presentation, are given anterior chemotherapy, three to four cycles to downstage and make the tumour operable. Once this is achieved, surgery is performed, followed by radiotherapy and remaining cycles of chemotherapy.
Chemotherpay regimes and indications for hormonal treatment are same as in early Ca Breast.
Patients with Supraclavicular Nodal Metastasis are  treated as LABC. Anterior chemotherapy is given and once the supraclavicular nodes regress, the patient is offered surgery and radiotherapy.and remaining chemotherapy
Two to three cycles of neoadjuvasnt chemotherapy may be given to even operable cases of LABC to prevent systemic spread
Metasatatic Carcinoma Breast
There is no role of surgery in patients presenting with metasatatic disease at time of diagnosis. Common sites for metastasis are liver, lungs, bone and brain.
These patient are managed with docitaxol based chemotherapy and hormonal treatment.
Patients with brain metastasis get cranial radiotherapy with or without tablet Timizolemide.
Patient with extensive bony metastasis require hemi or whole body radiation with monthly  injection pamidronate.
Local surgery or radiotherapy can be offered as a palliative measure, in case of pain, necrosis, ulceration, fungation or anxiety of patient for retaining the diseased breast.
Opherectomy by surgery or radiotherapy can be considered for premenopausal ladies with metastatic disease.
Recurrent Disease
Local recurrence after BCT needs mastectomy and recurrence over chest wall, following mastectomy is treated with wide local excision and local radiotherapy. Second line chemotherapy to be considered in all these cases.
Recurrent disease at distant sites is managed with salvage chemotherapeutic regimes like MMM (Mitomycin, Methotrexate and Mitoxantrone) and second or third line hormonal therapy with megace or femera . Other chemotherapeutic agents available are Liposomal Doxorubian, weekly epirubian ,Gemcitabine and Vinorelbine with Cisplatinum.   Herceptine to be used in reccurant or advanced metastatic cases, which are HER 2 positive.
Carcinoma Breast in Males
About once percent of breast cancers are found in males. The initial stage of presentation in males is higher than in females with a large number being diagnosed in Stage III. Management and prognosis is same as in females.Males may have lobular carcinoma too.  Tamoxifen is used in ER PR cases for hormonal manipulation.
Inflammatory Carcinoma Breast
This is an aggressive form of cancer breast seen in younger patients with extensive involvement of overlying skin and subcutaneous lymphatics. Managed as LABC with only change being that surgery is usually performed after chemotherapy and radiation.

Management of High Risk Patients
Patients with LCIS, strong family history, women who carry mutations in BRCA 1 or 2 and those with atypical hyperplasia on biopsy of breast tissue, are high risk patients.
These patients should be under close observation and annual mammography.
Follow up
Patient with Ca Breast should be observed closely after treatment for metastasis and second primary on opposite breast. Besides routine work up, they should undergo annual mammography of the opposite breast ,ultrasound pelvis for endometrial thicking  while on Tamoxifen, to rule out endometrial carcinoma and bone scan every 2 years

 
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