reference: shwartz

1. Dr. Ammar Alsulaiman

2. Histopathology Of Breast Cancer
Carcinoma in Situ
Invasive Breast Ca
Staging
Breast Ca Therapy

4.  Cancer cells are in situ or invasive depending on whether or not they
invade through the basement membrane.
 Multicentricity refers to the occurrence of a second breast cancer
outside the breast quadrant of the primary cancer (or at least 4 cm
away).
 Multifocality refers to the occurrence of a second cancer within the
same breast quadrant as the primary cancer (or within 4 cm of it).
 Multicentricity occurs in 60% to 90% of women with LCIS, whereas
the rate of multicentricity for DCIS is reported to be 40% to 80%.
 LCIS occurs bilaterally in 50% to 70% of cases, whereas DCIS occurs
bilaterally in 10% to 20% of cases.

5.  LCIS originates from the terminal duct lobular units and develops only in
the female breast.
 Cytoplasmic mucoid globules are a distinctive cellular feature.
 LCIS may be observed in breast tissues that contain microcalcifications,
but the calcifications associated with LCIS typically occur in adjacent
tissues. This neighborhood calcification is a feature that is unique to
LCIS.
 The average age at diagnosis is 45 years, which is approximately 15 to 25
years younger than the age at diagnosis for invasive breast cancer.
 It is 12 times more frequently in white women than in African-American
women.

7.  Histologically, DCIS is characterized by a proliferation of the epithelium that lines the
minor ducts, resulting in papillary growths within the duct lumina.
 Early in their development, the cancer cells do not show pleomorphism, mitoses, or
atypia, which leads to difficulty in distinguishing early DCIS from benign hyperplasia.
 The papillary growths (papillary growth pattern) eventually merge and fill the duct
lumina so that only scattered, rounded spaces remain between the clumps of atypical
cancer cells, which show hyperchromasia and loss of polarity (cribriform growth
pattern).
 Eventually pleomorphic cancer cells with frequent mitotic figures obliterate the
lumina and distend the ducts (solid growth pattern).
 With continued growth, these cells outstrip their blood supply and become necrotic
(comedo growth pattern). Calcium deposition occurs in the areas of necrosis and is a
common feature seen on mammography.
 The risk for invasive breast cancer is increased nearly fivefold in women with DCIS.

10.  Foote and Stewart originally proposed the following classification for invasive breast
cancer:
 1. Paget’s disease of the nipple
 2. Invasive ductal carcinoma—Adenocarcinoma with productive fibrosis (scirrhous,
simplex, NST), 80%
 3. Medullary carcinoma, 4%
 4. Mucinous (colloid) carcinoma, 2%
 5. Papillary carcinoma, 2%
 6. Tubular carcinoma, 2%
 7. Invasive lobular carcinoma, 10%
 8. Rare cancers (adenoid cystic, squamous cell, apocrine)

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 It frequently presents as a chronic, eczematous
eruption of the nipple, which may be subtle but may
progress to an ulcerated, weeping lesion.
 Paget’s disease usually is associated with extensive
DCIS and may be associated with an invasive cancer.
 A palpable mass may or may not be present.
 Pathognomonic of this cancer is the presence of large,
pale, vacuolated cells (Paget cells).
 Surgical therapy for Paget’s disease may involve
lumpectomy or mastectomy.

12.  Presents with macroscopic or microscopic axillary lymph node
metastases in up to 25% of screen-detected cases and up to 60% of
symptomatic cases.
 This cancer occurs most frequently in perimenopausal or
postmenopausal women in the fifth to sixth decades of life as a
solitary, firm mass.
 It has poorly defined margins, and its cut surfaces show a central
stellate configuration with chalky white or yellow streaks extending
into surrounding breast tissues.

13.  IT is a frequent phenotype of BRCA1 hereditary breast cancer.
 Grossly, the cancer is soft and hemorrhagic.
 Approximately 50% of these cancers are associated with DCIS,
which characteristically is present at the periphery of the cancer,
and <10% demonstrate hormone receptors.
 Women with this cancer have a better 5-year survival rate than
those with NST or invasive lobular carcinoma.

14. Typically presents in the older population as a bulky
tumor.
This cancer is defined by extracellular pools of mucin,
which surround aggregates of low-grade cancer cells.
Over 90% of mucinous carcinomas display hormone
receptors.
Lymph node metastases occur in 33% of cases, and 5- and
10-year survival rates are 73% and 59%, respectively.

15. Usually, they are small and rarely attain a size of 3 cm in
diameter.
These cancers are defined by papillae with fibrovascular
stalks and multilayered epithelium.
these tumors showed a low frequency of axillary lymph
node metastases and had 5- and 10-year survival rates
similar to those for mucinous and tubular carcinoma.

16. Diagnosed in the perimenopausal or early menopausal
periods.
94% of tubular cancers were reported to express estrogen
receptor.
Approximately 10% of women with tubular carcinoma will
develop axillary lymph node metastases. However, the
presence of metastatic disease in one or two axillary
lymph nodes does not adversely affect survival.
Long-term survival approaches 100%.

17. Presence of intracytoplasmic mucin, which may displace
the nucleus (signet-ring cell carcinoma).
It is frequently multifocal, multicentric, and bilateral.
Because of its insidious growth pattern and subtle
mammographic features, invasive lobular carcinoma may
be difficult to detect.
Over 90% of lobular cancers express estrogen receptor

24. Once a diagnosis of breast cancer is made, the type of
therapy offered to a breast cancer patient is determined by
the stage of the disease, the biologic subtype, and the general
health status of the individual.

25.  Bilateral mammography is performed to determine the extent of the in-
situ cancer and to exclude a second cancer.
 Because LCIS is considered a marker for increased risk rather than an
inevitable precursor of invasive disease, the current treatment options for
LCIS include observation, chemoprevention, and bilateral total
mastectomy.
 There is NO benefit to excising LCIS because the disease diffusely involves
both breasts in many cases and the risk of developing invasive cancer is
equal for both breasts.
 The use of tamoxifen as a risk-reduction strategy should be considered.
 Women with DCIS and evidence of extensive disease (>4 cm of disease or
disease in more than one quadrant) usually require mastectomy.
 For women with limited disease, lumpectomy and radiation therapy are
generally recommended.

26.  Women treated with mastectomy have local recurrence and
mortality rates of <2%.
 Women treated with lumpectomy and adjuvant radiation therapy in
the initial clinical trials were noted to have a local recurrence rate
that is increased compared to mastectomy.
 About 45% of these recurrences will be invasive cancer when
radiation therapy is not used.
 a 2-mm margin was determined as adequate width for DCIS for
patients undergoing breast-conserving surgery with whole-breast
radiation therapy.

27.  Silverstein and colleagues were proponents of avoiding radiation
therapy in selected patients with DCIS who have widely negative
margins after surgery.
 They reported that when greater than 10-mm margins were
achieved, there was no additional benefit from radiation therapy.
 When margins were between 1 and 10 mm, there was a relative risk
of local recurrence of 1.49, compared to 2.54 for those with margins
less than 1 mm.
 These data suggested that appropriately selected patients with
DCIS might not require postoperative radiation therapy.

28.  The Eastern Cooperative Oncology Group (ECOG) initiated a prospective
registry trial to identify those patients who could safely undergo breast-
conserving surgery without radiation.
 Eligible patients were those with low or intermediate grade DCIS
measuring 2.5 cm or less who had negative margins of at least 3 mm and
those with high-grade DCIS who had tumors measuring 1 cm or less with
a negative margin of at least 3 mm.
 At a median follow-up of 6.2 years, patients with low or intermediate
grade DCIS had an in-breast recurrence rate of 6.1% while those with
high-grade DCIS had a recurrence rate of 15.3%.
 Approximately 4% of patients developed a contralateral breast cancer
during follow-up in both the low/intermediate and high-grade groups.

29.  The Radiation Therapy Oncology Group (RTOG) initiated a trial for
patients with “good risk” DCIS and randomized them to lumpectomy vs.
lumpectomy with whole breast irradiation.
 The local recurrence rate at 5 years was 0.4% for patients randomized
to receive radiation and 3.2% for those who did not receive radiation.
 Results from theB-24 trial reported a significant reduction in local
recurrence after 5 years of tamoxifen in women with ER-positive DCIS.
 Based on this finding, some guidelines have advocated that all patients
should be offered tamoxifen following surgery and radiation therapy for
a duration of 5 years.

30.  B-06, which is the largest of all the breast conservation trials,
compared total mastectomy to lumpectomy with or without
radiation therapy in the treatment of women with stages I and II
breast cancer.
 After 5- and 8-year follow-up periods, the disease-free (DFS), distant
disease- free, and overall survival (OS) rates for lumpectomy with or
without radiation therapy were similar to those observed after total
mastectomy.
 These findings supported the use of lumpectomy and radiation
therapy in the treatment of stages I and II breast cancer, and this
has since become the preferred method of treatment for women with
early-stage breast cancer who have unifocal disease and who are not
known BRCA mutation carriers.

31.  The Cancer and Leukemia Group B (CALGB) trial enrolled women
over the age of 70 with T1N0 breast cancer and randomized them to
lumpectomy with or without radiation therapy.
 All patients received adjuvant tamoxifen.
 At 5 years there were fewer local recurrences with radiation (1% vs.
4%, P <0.001), there were no differences in DFS and OS.
 TARGIT is another study that randomized patients to intraoperative
breast irradiation (IORT) or external beam radiotherapy (EBRT).
 The results were reported in 2012: with a median follow-up of 2.4
years, use of IORT had a recurrence rate of 3.3% vs. 1.3% with
EBRT, a 2% increased recurrence risk.

32.  Breast conservation is considered for all patients because of the
important cosmetic advantages and equivalent survival outcomes;
 however, this approach is not advised in women who are known
BRCA mutation carriers due to the high lifetime risk for
development of additional breast cancers.
 Relative contraindications include
(a) prior radiation therapy to the breast or chest wall,
(b) persistently positive surgical margins after reexcision,
(c) multicentric disease,
(d) scleroderma or lupus erythematosus.

33.  The ALMANAC trial randomized 1031 patients with primary
operable breast cancer to SLN dissection vs. standard axillary
surgery.
 The incidence of lymphedema and sensory loss for the SLN group
was significantly lower than with the standard axillary treatment.
 At 12 months, drain usage, length of hospital stay, and time to
resumption of normal day-to-day activities after surgery were also
statistically significantly lower in the SLN group

34.  The results of Z0010 and B-32 showed no clinically meaningful
difference in survival based on detection of occult metastases
in the SLNs using immunohistochemical staining and do not
support the routine use in SLN processing.
 The Z0011 trial was a companion study to Z0010 and was
designed to study the role of completion ALND on survival in
women with positive SLNs. After median follow-up of 6.3
years, there was no difference between patients randomized to
ALND and those randomized to no further surgery (SLN only).

35.  The ASCO guidelines suggest that adjuvant chemotherapy should
be considered for patients with positive lymph nodes, ER-negative
disease, HER2-positive disease, Adjuvant endocrine therapy is
considered for women with hormone receptor-positive cancers, and
an aromatase inhibitor is recommended if the patient is
postmenopausal.
 HER2/ neu status is determined for all patients with newly
diagnosed invasive breast cancer and when positive, should be used
to guide systemic therapy recommendations.
 The FDA approved Trastuzumab for use as part of a treatment
regimen containing doxorubicin, cyclophosphamide, and paclitaxel
for treatment of HER2/neu-positive, node-positive breast cancer.

36.  Women with stage IIIA and IIIB breast cancer have advanced local-regional
breast cancer but have no clinically detected distant metastases.
 Neoadjuvant chemotherapy should be considered in the initial management of
patients with stage III breast cancer.
 Chemotherapy is used to maximize distant disease-free survival, whereas
radiation therapy is used to maximize local-regional control and disease-free
survival.
 Investigators from the MD Anderson Cancer Center reported that low local-
regional failure rates could be achieved in selected patients with stage III
disease treated with preoperative chemotherapy followed by breast-conserving
surgery and radiation.
 The 5-year ipsilateral breast tumor recurrence-free survival rates in this
study were 95%.

37.  The German Breast Cancer Group recently reported their local
recurrence rate in 5535 patients in seven studies. With a median of
46 months follow-up
 the local recurrence rates ranged from 7.6% to 19.5% for T1-T4
tumors and from 6.4% to 17.9% for N0-N3 tumors treated with
neoadjuvant therapy.
 A series of 195 patients with ER-positive, locally advanced breast
cancer treated by endocrine therapy—median age 69 years, median
tumor size 6 cm, median follow-up 61 months—reported a 5-year
overall survival of 76%, a breast cancer–specific survival of 86%, and
a metastasis-free survival of 77%.

38.  Results from the Z1031 trial suggest that neoadjuvant endocrine
therapy is a good option for tumor downstaging in patients with
strongly ER-positive tumors.
 The preoperative endocrine prognostic index (PEPI score) can be
calculated based on pathologic findings from surgery following
neoadjuvant endocrine therapy. This can help guide decision making
regarding the need for systemic chemotherapy in this patient
population.

39.  Treatment for stage IV breast cancer is not curative but may prolong
survival and enhance a woman’s quality of life.
 Endocrine therapies that are associated with minimal toxicity are
preferred to cytotoxic chemotherapy in ER-positive disease.
 Appropriate candidates for initial endocrine therapy include women
with hormone receptor-positive cancers who do not have
immediately life-threatening disease (or “visceral crisis”).
 This includes not only women with bone or soft tissue metastases
but also women with limited visceral metastases.

41.  Systemic chemotherapy is indicated for women with hormone
receptor-negative cancers, “visceral crisis,” and hormone-refractory
metastases.
 Bisphosphonates or anti- RANKL (receptor activator of nuclear
factor kappa-B ligand) agent, denosumab, which may be given in
addition to chemotherapy or endocrine therapy, should be considered
in women with bone metastases.
 Whether to perform surgical resection of the local-regional disease in
women with stage IV breast cancer has been debated after several
reports have suggested that women who undergo resection of the
primary tumor have improved survival over those who do not.

42. Women treated previously with mastectomy undergo
surgical resection of the local-regional recurrence and
appropriate reconstruction.
Women treated previously with a breast-conservation
procedure undergo a mastectomy and appropriate
reconstruction.

43.  The overall 5-year relative survival for breast
cancer patients from the time period of 2003 to
2009 from 18 SEER geographic areas was 89.2%.
 The 5-year relative survival by race was reported
to be 90.4% for white women and 78.7% for black
women.
 The 5-year survival rate for patients with:
 localized disease (61% of patients) is 98.6%;
 Patients with regional disease (32% of patients),
84.4%;
 Patients with distant metastatic disease (5% of
patients), 24.3%.

44. Schwartz textbook of surgery 11th
edition.